Top ▲

FPR2/ALX

Click here for help

Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 223

Nomenclature: FPR2/ALX

Family: Formylpeptide receptors, Leukotriene receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 351 19q13.41 FPR2 formyl peptide receptor 2 4,69
Mouse 7 351 17 A3.2 Fpr2 formyl peptide receptor 2 34,96
Rat 7 351 1q12 Fpr2 formyl peptide receptor 2 14,68
Previous and Unofficial Names Click here for help
ALXR | FMLPX | FPRH1 | LXA4R | ALX | FPRH2 | FPRL1 | RFP | formyl peptide receptor-like 1 | formyl peptide receptor 2 | formyl peptide receptor, related sequence 2 | Fpr-rs2 | ALX/FPR2 | FPR2A
Database Links Click here for help
Specialist databases
GPCRdb fpr2_human (Hs), fpr2_mouse (Mm)
Other databases
Alphafold P25090 (Hs), O88536 (Mm)
ChEMBL Target CHEMBL4227 (Hs), CHEMBL4739842 (Mm)
Ensembl Gene ENSG00000171049 (Hs), ENSMUSG00000052270 (Mm), ENSRNOG00000042605 (Rn)
Entrez Gene 2358 (Hs), 14289 (Mm), 690158 (Rn)
Human Protein Atlas ENSG00000171049 (Hs)
KEGG Gene hsa:2358 (Hs), mmu:14289 (Mm), rno:690158 (Rn)
OMIM 136538 (Hs)
Pharos P25090 (Hs)
RefSeq Nucleotide NM_001462 (Hs), NM_008042 (Mm)
RefSeq Protein NP_001453 (Hs), NP_032068 (Mm)
UniProtKB P25090 (Hs), O88536 (Mm)
Wikipedia FPR2 (Hs)
Natural/Endogenous Ligands Click here for help
annexin I {Sp: Human} , annexin I {Sp: Mouse} , annexin I {Sp: Rat}
aspirin triggered lipoxin A4
aspirin-triggered resolvin D1
CRAMP {Sp: Mouse}
humanin {Sp: Human}
LL-37 {Sp: Human}
LXA4
PrP106-126
resolvin D1
serum amyloid A {Sp: Human}
Potency order of endogenous and other ligands
LXA4 = aspirin triggered lipoxin A4 = ATLa2 = resolvin D1 > LTC4 = LTD4 >> 15-deoxy-LXA4 >> fMet-Leu-Phe  [17,26,29,39,96]

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
WKYMVm Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 10.1 pKd 15,43,45,58
⤷ pKd 10.1 [15,43,45,58]
[3H]LXA4 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 9.1 – 9.3 pKd 26,28
⤷ pKd 9.1 – 9.3 (Kd 7x10-10 – 5x10-10 M) [26,28]
LXA4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Partial agonist 8.8 – 9.3 pKd 26,28
⤷ pKd 8.8 – 9.3 [26,28]
[3H]LXA4 Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Full agonist 8.8 pKd 96
⤷ pKd 8.8 (Kd 1.5x10-9 M) [96]
[3H]LXA4 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Full agonist 8.3 pKd 14
⤷ pKd 8.3 (Kd 5x10-9 M) [14]
annexin I {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 6.5 pKd 75
⤷ pKd 6.5 [75]
fMet-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 6.4 pKd 81
⤷ pKd 6.4 [81]
[125I-Tyr]Ac2-26 Peptide Ligand is labelled Ligand is radioactive Rn Full agonist 6.1 pKd 14
⤷ pKd 6.1 (Kd 8.2x10-7 M) [14]
[125I-Tyr]Ac2-26 Peptide Ligand is labelled Ligand is radioactive Hs Agonist 5.9 pKd 75
⤷ pKd 5.9 (Kd 1.3x10-6 M) [75]
CGEN-855A Peptide Hs Full agonist 7.3 pKi 46
⤷ pKi 7.3 (Ki 5.41x10-8 M) [46]
LXA4 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist ~12.0 pEC50 54
⤷ pEC50 ~12.0 (EC50 ~1.1x10-12 M) [54]
resolvin D1 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Full agonist ~11.9 pEC50 54
⤷ pEC50 ~11.9 (EC50 ~1.2x10-12 M) [54]
RvD1-ME Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 11.4 pEC50 53
⤷ pEC50 11.4 (EC50 3.7x10-12 M) [53]
aspirin-triggered resolvin D1 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Full agonist 11.1 pEC50 53
⤷ pEC50 11.1 [53]
WKYMVm Peptide Click here for species-specific activity table Immunopharmacology Ligand Mm Full agonist 9.0 – 10.1 pEC50 43,45
⤷ pEC50 9.0 – 10.1 [43,45]
BMS-986235 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Mm Agonist 9.3 pEC50 2
⤷ pEC50 9.3 (EC50 5x10-10 M) [2]
sCKβ8-1 Peptide Hs Full agonist 8.9 – 9.1 pEC50 24
⤷ pEC50 8.9 – 9.1 [24]
MMK-1 Peptide Immunopharmacology Ligand Hs Full agonist 8.7 pEC50 47,51
⤷ pEC50 8.7 [47,51]
PSMα3 Peptide Hs Full agonist 8.7 pEC50 52
⤷ pEC50 8.7 [52]
ACT-389949 Small molecule or natural product Immunopharmacology Ligand Hs Agonist 8.5 pEC50 92
⤷ pEC50 8.5 (EC50 3x10-9 M) [92]
Description: FPR2/ALX internalization into monocytes.
humanin {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.5 pEC50 41
⤷ pEC50 8.5 [41]
BMS-986235 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 8.3 pEC50 2
⤷ pEC50 8.3 (EC50 5x10-9 M) [2]
fMet-Met-Tyr-Ala-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 7.8 pEC50 82
⤷ pEC50 7.8 [82]
SHAAGtide Peptide Hs Full agonist 7.7 pEC50 24,66
⤷ pEC50 7.7 [24,66]
pyrazolone, 1 Small molecule or natural product Ligand has a PDB structure Hs Full agonist 7.4 pEC50 9
⤷ pEC50 7.4 [9]
T21/DP107 Peptide Hs Full agonist 7.3 pEC50 94
⤷ pEC50 7.3 (EC50 5x10-8 M) [94]
uPar fragment Peptide Hs Full agonist 7.1 pEC50 83
⤷ pEC50 7.1 [83]
amyloid β {Sp: Human} Peptide Hs Full agonist 7.0 pEC50 59,97
⤷ pEC50 7.0 [59,97]
pyrazolone, 1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Full agonist 6.9 pEC50 43
⤷ pEC50 6.9 [43]
CRAMP {Sp: Mouse} Peptide Ligand is endogenous in the given species Immunopharmacology Ligand Mm Full agonist 6.7 – 7.0 pEC50 56
⤷ pEC50 6.7 – 7.0 [56]
fMet-Ile-Val-Thr-Leu-Phe Peptide Click here for species-specific activity table Hs Full agonist 6.7 pEC50 82
⤷ pEC50 6.7 [82]
serum amyloid A {Sp: Human} Peptide Ligand is endogenous in the given species Hs Full agonist 6.6 pEC50 95
⤷ pEC50 6.6 (EC50 2.5x10-7 M) [95]
humanin {Sp: Human} Peptide Mm Full agonist 6.0 – 7.0 pEC50 103
⤷ pEC50 6.0 – 7.0 [103]
F2L {Sp: Human} Peptide Mm Full agonist 6.4 pEC50 35
⤷ pEC50 6.4 (EC50 4x10-7 M) [35]
AG-26 Small molecule or natural product Hs Full agonist 6.3 pEC50 50
⤷ pEC50 6.3 [50]
compound R-(-)-5f [PMID: 22607879] Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.3 pEC50 16
⤷ pEC50 6.3 (EC50 5.4x10-7 M) [16]
quin-C1 Small molecule or natural product Mm Full agonist 6.2 pEC50 43
⤷ pEC50 6.2 [43]
LL-37 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand Hs Full agonist 6.0 pEC50 19
⤷ pEC50 6.0 [19]
annexin I-(2-26) {Sp: Human} Peptide Click here for species-specific activity table Hs Full agonist 5.8 – 6.1 pEC50 36,42,75,99
⤷ pEC50 5.8 – 6.1 [36,42,75,99]
quin-C1 Small molecule or natural product Hs Full agonist 5.7 pEC50 70
⤷ pEC50 5.7 [70]
fMet-Ile-Val-Thr-Leu-Phe Peptide Click here for species-specific activity table Mm Full agonist 5.6 pEC50 43,91
⤷ pEC50 5.6 [43,91]
fMet-Met-Tyr-Ala-Leu-Phe Peptide Click here for species-specific activity table Mm Full agonist 5.3 pEC50 43
⤷ pEC50 5.3 [43]
PrP106-126 Peptide Ligand is endogenous in the given species Hs Agonist 4.6 pEC50 10
⤷ pEC50 4.6 [10]
MHC binding peptide Peptide Hs Full agonist 10.0 pIC50 12
⤷ pIC50 10.0 [12]
CGEN-855A Peptide Hs Full agonist 6.7 pIC50 46
⤷ pIC50 6.7 (IC50 1.89x10-7 M) [46]
Hp(2-20) Peptide Click here for species-specific activity table Hs Agonist - - 5
⤷ [5]
N36 Peptide Hs Full agonist - - 60
⤷ [60]
F peptide Peptide Hs Full agonist - - 20
⤷ [20]
V3 peptide Peptide Hs Full agonist - - 86
⤷ [86]
1R-11 Small molecule or natural product Immunopharmacology Ligand Hs Agonist - - 18
⤷ [18]
View species-specific agonist tables
Agonist Comments
Listed above are major FPR2/ALX agonists and several agonists for mouse Fpr2 (Fpr-rs2). They are grouped into several classes:
1. Bacteria-derived formyl peptides: The classic tripeptide fMet-Leu-Phe is a low affinity agonist for FPR2/ALX and is not an activator for mouse Fpr2. The PSMα3 peptide from highly pathogenic S. aureus has a pEC50 value of 8.67 and is one of the most potent bacterial formyl peptides for FPR2/ALX.
2. Mitochondria-derived formyl peptides: fMet-Met-Tyr-Ala-Leu-Phe (ND6), fMet-Leu-Lys-Leu-Ile-Val (ND4), and fMet-Tyr-Phe-Ile-Asn-Ile-Leu-Thr-Leu (ND1) are endogenous agonists for FPR2/ALX [82].
3. Lipid mediators: resolvin D1 (RvD1) and lipoxin A4 (LXA4). LXA4 is highly potent in triggering anti-inflammatory functions in animal models. Cell-based studies suggest that FPR2/ALX is a receptor for LXA4 in several published reports [13,26,28], but others failed to identify LXA4-induced GPCR responses [31,40,78]. One of the reasons could be agonist (LXA4) batch difference. A recent study [54] showed that RvD1 and LXA4 selectively activate the beta-arrestin pathway, suggesting that RvD1 and LXA4 might be partial agonists or biased agonists at ALX/FPR2. See [40] for a different outcome in β-arrestin translocation by LXA4.
4. Host-derived non-amyloidogenic peptides: This class includes SHAAGtide, LL-37, CCL-23, humanin, and uPAR(88-274)/D2D3. Annexin and derived peptides are also host-derived non-amyloidogenic peptides, but some of these peptides are less selective between FPR1 and FPR2/ALX.
5. Host-derived amyloidogenic peptides: SAA and Aβ[1-42] are two agonists in this class. They also bind and activate other receptors.
6. HIV-1 envelope peptides: These are T21/DP107, N36, F peptide, and V3 peptide.
7. Prion peptide: PrP (106-126) is the only member of this class, derived from prion proteins.
8. Peptides identified from library screen: This class is represented by WKYMVm and MMK-1. Other peptides with lower potency or affinity are not shown.
9. Synthetic compounds which are FPR2/ALX-specific agonists: Quin-C1, N`-Phenylurea derivatives (AG-26, AG-09/37, AG-09/38, AG-09/42, and AG-09/43), 2-(N-piperazinyl) acetamide derivatives (AG-09/3, AG-09/4, AG-09/73 through AG-09/77, and AG-09/82), and acetohydrazide derivatives (AG-09/7, AG-09/92, AG-09/96, AG-09/101, and AG-09/102). Selected chiral 6-methyl-2, 4-disubstituted pyridazin-3(2H)-compounds are potent mixed FPR1/FPR2/ALX agonists, among which R-(-)-forms generally exhibited higher activity than the S-(+)-enantiomers [16]. Pyrazolone, 4-iodo-substituted compound no. 43 activates FPR2/ALX and mouse Fpr1.

Mouse Fpr2 shares most of its binding properties with human FPR2/ALX. One of the differences is the inability for the mouse Fpr2 to bind and interact with most formylpeptides tested. The exceptions are long peptides such as fMLFII, fMMYALF (from mitochondria), fMIVIL (from L. monocytogenes), which are better agonists with reasonably good EC50 in most functional assays.

Hp(2-20), a peptide from H. pylori induced a rise in intracellular calcium levels in cells tranfected with FPR2/ALX; however the efficacy of this peptide was greater at FPRL2-expressing cells [5].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
quin-C7 Small molecule or natural product Hs Antagonist 5.2 pEC50 104
⤷ pEC50 5.2 [104]
isopropylureido-FLFLF Peptide Hs Antagonist 4.3 – 6.0 pEC50 21
⤷ pEC50 4.3 – 6.0 [21]
compound 1754-31 [PMID: 23788657] Small molecule or natural product Hs Antagonist 7.1 pIC50 77
⤷ pIC50 7.1 [77]
WRWWWW Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 6.6 pIC50 3
⤷ pIC50 6.6 [3]
t-Boc-FLFLF Peptide Click here for species-specific activity table Hs Antagonist 4.3 – 6.0 pIC50 32,93,99
⤷ pIC50 4.3 – 6.0 [32,93,99]
FPRL1-inhibitor protein Peptide Hs Antagonist - - 79
⤷ [79]
Antagonist Comments
The available FPR2/ALX antagonists are very limited at this time. The recently identified compound (1754-31) is one of the most potent FPR2/ALX antagonists. None of the FPR2/ALX antagonists are found to have inverse agonistic activity. t-Boc-FLFLF is shown in some publications as an antagonist for both FPR1 and FPR2/ALX. In a recent publication, its antagonistic activity is found to be more selective for FPR1 than FPR2/ALX [71].
Allosteric Modulators
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PBP10 Peptide Hs Positive 7.0 pIC50 82
⤷ pIC50 7.0 [82]
Allosteric Modulator Comments
PBP10 is a cell-permeable, rhodamine B-coupled polyphosphoinositide-binding peptide based on gelsolin a.a. 160-169. PBP10 inhibits neutrophil degranulation and superoxide generation induced by FPR2/ALX agonists but not FPR1 agonists. However, PBP10 does not affect agonist-induced calcium mobilization, suggesting that it is an allosteric modulator of FPR2/ALX mediated functions [30,33].
Immunopharmacology Comments
Formyl peptide receptor type 2 (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. Resolvin D1-mediated activation of FPR2/ALX appears to resolve salivary gland inflammation in a mouse model of Sjögren syndrome [100]. FPR2/ALX receptor agonism is a new therapeutic concept that is being investigated for the development of novel non-steroidal anti-inflammatory agents as modulators of pathological dysregulated inflammation [6-7]. Since endogenous pro-resolving mediators like lipoxin A4 are highly unstable, investigators are designing lipoxin mimetics with improved physicochemical properties [18].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Antigen presentation
Immuno Process:  Immune regulation
Immuno Process:  Chemotaxis & migration
Immuno Process:  Cellular signalling
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Phospholipase C stimulation
Phospholipase A2 stimulation
Phospholipase D stimulation
References:  26-27,48,57,73-74
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  FPR2/ALX joins a small group of chemoattractant/chemokine receptors which share a mechanism of using CD38-dependent cyclic ADP ribose for calcium flux and chemotaxis. Many of these receptors also couple to Gq in addition to Gi proteins.
References:  73-74
Tissue Distribution Click here for help
Most abundant in the lung, followed by spleen and placenta, tissues known to have a relatively high degree of phagocytic cell infiltrates.
Species:  Human
Technique:  Northern blot
References:  26,96
Cloned in several types of leukocytes, including PMN, monocytes and T cells, as well as resident cells such as macrophages, synovial fibroblasts and intestinal epithelial cells.
Species:  Human
Technique:  RT-PCR
References:  13
Human FPR2/ALX is expressed in neutrophils, monocytes, macrophages, immature dendritic cells, and at low levels in T and B cells. FPR2/ALX is also found in epithelial cells, mocroglial cells, astrocytes, hepatocytes, and at low levels in endothelial cells.
Species:  Human
Technique:  RT-PCR
References:  67
Most abundant in neutrophils, followed by spleen and lung.
Species:  Mouse
Technique:  Northern blot
References:  96
Expressed in lung, kidney and leukocytes.
Species:  Rat
Technique:  RNase protection assay
References:  14
Expression Datasets Click here for help

Show »

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays Click here for help
Calcium mobilization, adherence, chemotaxis
Species:  Human
Tissue:  Monocyte, THP-1 cells
Response measured:  LXA4 increases calcium mobilization, adherence, chemotaxis
References:  64-65
ERK activation
Species:  Human
Tissue:  T cells
Response measured:  ATL stimulate ERK activation
References:  1
IL-8 gene expression and release, NF-κB activation
Species:  Human
Tissue:  Enterocyte
Response measured:  LXA4 and ATL reduce IL-8 and NF-κB activation
References:  37,55
Phagocytosis
Species:  Human
Tissue:  Macrophage
Response measured:  LXA4 stimulates nonphlogistic phagocytosis of apoptotic neutrophils
References:  38
LXA4 reduces IL-8 and NF-κB responses, alters MMP-1 and MMP-3 expression
Species:  Human
Tissue:  Fibroblast
Response measured: 
References:  88-89
PLD activation, arachidonic acid release, PSDP increase
Species:  Human
Tissue:  PMN, HL-60 cells or CHO cells overexpressing human FPR2/ALX
Response measured:  LXA4 and ATL stimulate PLD activation, arachidonic acid release, PSDP, inhibits superoxide anion generation
References:  26-28,62
Physiological Functions Click here for help
Superoxide generation. Some of the FPR2/ALX agonists are known to stimulate neutrophil superoxide generation. This function can play a role in both host defense and tissue injury.
Species:  Human
Tissue:  Neutrophils, monocytes, macrophages
References:  85
Induction of inflammatory gene expression. Several FPR2/ALX agonists have been shown to stimulate NF-κB activation, resulting in the expression of proinflammatory cytokines and metalloproteinases. This activity is FPR2/ALX dependent.
Species:  Human
Tissue:  Neutrophils, synovial fibroblasts, chondrocytes
References:  44,61,89
Chemotaxis. Nearly all FPR2/ALX agonists induce chemotaxis either in neutrophils and monocytes that naturally express this receptor or in FPR2/ALX transfected cell lines. This function is responsible for cell migration, neutrophil and monocyte accumulation in vivo.
Species:  Human
Tissue:  Neutrophils, monocytes, other leukocytes that express FPR2
References:  58,95
LXA4 and ATL regulate gene expression in synovial fibroblasts (e.g. IL-1b, IL-6, IL-8, MMP-1, MMP-3), and in epithelial cells (e.g. IL-8, NF-κB).
Species:  Human
Tissue:  Fibroblast, enterocyte
References:  37,55,88-89
LXA4 and ATL give pro-resolving signals, stimulating non-phlogistic monocyte activation (clacium mobilization, adherence and chemotaxis), and macrophage phagocytosis of apoptotic PMN
Species:  Human
Tissue:  Monocyte and macrophage
References:  38,64-65
LXA4 and ATL give anti-inflammatory signals such as reducing CD11b/CD18, expression, blocking ROS production, NF-κB activation, pro-inflammatory cytokines/chemokines. They also increase anti-inflammatory cytokines/chemokines and transcription corepressor NAB1
Species:  Human
Tissue:  Neutrophils
References:  25,29,80
Anti-inflammatory effect. Several studies have shown that ligands for FPR2/ALX such as LXA4, annexin I peptides and a synthetic small molecule, display anti-inflammatory effects in vivo and in vitro. While some of these effects may result in part from activation of other receptors such as AhR, transgenic expression of FPR2/ALX in mice has shown increased inhibiton of neutrophil infiltration and suppression of TNF-α induced NF-κB activity. A double-blinded, placebo-controlled, randomized clinical trial with 60 patients showed that 15(R/S)-methyl-LXA4 significantly reduced the severity of eczema (Wu et al, 2013).
Species:  Human
Tissue:  Ear skin, synovial fibroblasts
References:  9,22,75,90
Physiological Consequences of Altering Gene Expression Click here for help
Actions of RvD1 in reducing PMN infiltration and regulating select microRNAs were abolished in Fpr2 null mice
Species:  Mouse
Tissue:  Peritoneal exudate
Technique:  Gene knockouts
References:  53,72
Excerbated inflammation (ischemia reperfusion and arthritis). Fpr2 knockout mice exhibit an increased number of adherent and emigrated leukocytes after mesentery ischemia-reperfusion, whereas the number of platelet/neutrophil aggregates were decreased. Fpr2 knockout mice also exhibited an increased carrageenan-induced paw edema and exacerbation and prolongation of K/BxN serum-induced arthritis.
Species:  Mouse
Tissue: 
Technique:  Gene knockouts
References:  8,23
Deficiency in mFpr1 and mFpr2 exacerbated the severity of the infection and increased the mortality of infected mice. The mechanism involved impaired early neutrophil recruitment to the liver with Fpr1 and Fpr2 being sole receptors for neutrophils to sense Listeria chemoattractant signals and for production of bactericidal superoxide.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  63
Overexpression of human FPR2/ALX in transgenic mice results in an increased ability of LXA4 to attenuate neutrophil infiltration to ear skin tissue that are stimulated with LTB4 and PGE2. Mice also display a profound anti-inflammatory phenotype, markedly decreasing PMN infiltration with endogenous LXA4. Moreover, these hFPR2/ALX mice show increased sensitivity in response to the suboptimal doses of exogenous ATLa in vivo, shifting the dose response curve to the left when compared to their non-transgenic littermates. These results provide the compelling evidence for direct functional links between LXA4 and functional roles for human FPR2/ALX in vivo
Species:  Mouse
Tissue:  Peritoneal leukocytes
Technique:  Gene over-expression of human ALX/FPR2 in transgenic mice
References:  22
Fpr2 knockout mice exhibit reduced ovalbumin/alum-induced allergic airway inflammation, associated with lower levels of IL4, IL5 and IL13 in BAL and a reduced recruitment of dendritic cells to draining lymph nodes.
Species:  Mouse
Tissue:  Lung
Technique:  Gene knockouts
References:  11
Knockout of mouse FPR2/ALX (Fpr2), which shares structural and functional features of human FPR2/ALX, results in reduced responsiveness to F2L, an primary agonist for human FPR3.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  35
In vivo administration of 15-epi-LXA4 (aspirin triggered lipoxin A4) reduces intimal hyperplasia after vascular injury in wild-type mice, but is ineffective in Fpr2 knockout mice. Likewise, vascular smooth muscle cells derived from Fpr2 knockout mice are unresponsive to 15-epi-LXA4 in an in vitro wound healing assay.
Species:  Mouse
Tissue:  Blood vessels.
Technique:  Gene knockout.
References:  76
Xenobiotics Influencing Gene Expression Click here for help
Dexamethasone, prednisolone and triamcinolone up-regulate mRNA and protein levels of FPR2/ALX
Species:  Human
Tissue:  PMN, monocytes, lymphocytes, HL-60
Technique:  Flow cytometry, RT-PCR
References:  84
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0009278 abnormal bone marrow cell physiology PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0003009 abnormal cytokine secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0002376 abnormal dendritic cell physiology PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0002419 abnormal innate immunity PMID: 20200280 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6		 MGI:1278319  MP:0002463 abnormal neutrophil physiology PMID: 20107188 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0002281 abnormal respiratory mucosa goblet cell morphology PMID: 20200280 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6		 MGI:1278319  MP:0005164 abnormal response to injury PMID: 20107188 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0008127 decreased dendritic cell number PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0002492 decreased IgE level PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0008495 decreased IgG1 level PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0008497 decreased IgG2b level PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0002460 decreased immunoglobulin level PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0001876 decreased inflammatory response PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0008567 decreased interferon-gamma secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0008673 decreased interleukin-13 secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0008688 decreased interleukin-2 secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0008700 decreased interleukin-4 secretion PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0008703 decreased interleukin-5 secretion PMID: 20200280 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6		 MGI:1278319  MP:0003799 impaired macrophage migration PMID: 20107188 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0003799 impaired macrophage migration PMID: 20200280 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0008720 impaired neutrophil migration PMID: 20200280 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6		 MGI:1278319  MP:0005088 increased acute inflammation PMID: 20107188 
Fpr2tm1Rjf Fpr2tm1Rjf/Fpr2tm1Rjf
involves: 129S/SvEv * C57BL/6		 MGI:1278319  MP:0003724 increased susceptibility to induced arthritis PMID: 20107188 
Fpr2tm1.2Jimw Fpr2tm1.2Jimw/Fpr2tm1.2Jimw
B6.129X1-Fpr2		 MGI:1278319  MP:0002217 small lymph nodes PMID: 20200280 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Aspirin exacerbated respiratory diseases
References:  49
Disease:  Cardiovascular disease
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Single nucleotide polymorphism Human - A single nucleotide mutation (A/G) was detected in the core promoter of one subject with history of cardiovascular disease and of his two daughters 87
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Association of FPR2 polymorphisms and aspirin exacerbated respiratory diseases -- the minor allele frequency of FPR2 -4209T>G (rs1769490) in intron 2 was significantly lower in the AERD group (n=170) than in the ATA group (n=268). Asthmatic homozygotes for FPR2 -4209T>G minor allele exhibited significantly higher FPR2 protein expression in CD14-positive monocytes than did those with the common allele of FPR2 -4209T>G allele (P=0.01). There was no difference in the expression of the wild form and the exon 2 deleted variant form of FPR2 gene according to the genotypes of FPR2 -4209T>G. The minor allele at FPR2 -4209T>G may have a protective role against the development of AERD, via increase of ALX/FPR2 protein expression in inflammatory cells.
SNP accession:  rs1769490
References:  49
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The homozygous GG genotype of the FPRL1 -6136G>T polymorphism was significantly lower in subjects with chronic urticaria in a case control study.
References:  101
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A single nucleotide mutation (A/G) was detected in the core promoter of one subject with history of cardiovascular disease and of his two daughters. This mutation reduced ∼35-90% the promoter activity in vitro. Moreover, neutrophils from individuals carrying the A/G variant displayed ∼10- and 3-fold reduction in FPR2/ALX mRNA and protein, respectively, compared with cells from their relatives or healthy volunteers expressing the wild-type allele. These results uncover FPR2/ALX transcriptional regulation and provide the first evidence of mutations that affect ALX/FPR2 transcription, thus opening new opportunities for the understanding of the LXA4-FPR2/ALX axis in human disease.
References:  87
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The T-allele of a -7893C>T polymorphism of the FPRL1 gene was associated with coronary artery disease in a case-control study, but did not change the transcriptional activity of the gene promoter.
SNP accession:  rs56238033
References:  98
General Comments
The nomenclature for this receptor is outlined in the 2009 NC-IUPHAR review by Ye et al. [102].

It is important to validate chemical structures of LXA4, ATL and RvD1 before carrying out receptor assays because these ligands are chemically fragile and require precise working conditions at the bench. Also, it is noteworthy that LXA4 and RvD1 are subject to rapid metabolic conversion by mammalian cells and cell lines.

References

Show »

1. Ariel A, Chiang N, Arita M, Petasis NA, Serhan CN. (2003) Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-alpha secretion from human T cells. J Immunol, 170 (12): 6266-72. [PMID:12794159]

2. Asahina Y, Wurtz NR, Arakawa K, Carson N, Fujii K, Fukuchi K, Garcia R, Hsu MY, Ishiyama J, Ito B et al.. (2020) Discovery of BMS-986235/LAR-1219: A Potent Formyl Peptide Receptor 2 (FPR2) Selective Agonist for the Prevention of Heart Failure. J Med Chem, 63 (17): 9003-9019. [PMID:32407089]

3. Bae YS, Lee HY, Jo EJ, Kim JI, Kang HK, Ye RD, Kwak JY, Ryu SH. (2004) Identification of peptides that antagonize formyl peptide receptor-like 1-mediated signaling. J Immunol, 173 (1): 607-14. [PMID:15210823]

4. Bao L, Gerard NP, Eddy RL Jr, Shows TB, Gerard C. (1992) Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19. Genomics, 13: 437-440. [PMID:1612600]

5. Betten A, Bylund J, Christophe T, Cristophe T, Boulay F, Romero A, Hellstrand K, Dahlgren C. (2001) A proinflammatory peptide from Helicobacter pylori activates monocytes to induce lymphocyte dysfunction and apoptosis. J Clin Invest, 108 (8): 1221-8. [PMID:11602630]

6. Bozinovski S, Anthony D, Anderson GP, Irving LB, Levy BD, Vlahos R. (2013) Treating neutrophilic inflammation in COPD by targeting ALX/FPR2 resolution pathways. Pharmacol Ther, 140 (3): 280-9. [PMID:23880288]

7. Bozinovski S, Anthony D, Vlahos R. (2014) Targeting pro-resolution pathways to combat chronic inflammation in COPD. J Thorac Dis, 6 (11): 1548-56. [PMID:25478196]

8. Brancaleone V, Gobbetti T, Cenac N, le Faouder P, Colom B, Flower RJ, Vergnolle N, Nourshargh S, Perretti M. (2013) A vasculo-protective circuit centered on lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 operative in murine microcirculation. Blood, 122 (4): 608-17. [PMID:23733341]

9. Bürli RW, Xu H, Zou X, Muller K, Golden J, Frohn M, Adlam M, Plant MH, Wong M, McElvain M et al.. (2006) Potent hFPRL1 (ALXR) agonists as potential anti-inflammatory agents. Bioorg Med Chem Lett, 16 (14): 3713-8. [PMID:16697190]

10. Cattaneo F, Parisi M, Ammendola R. (2013) Distinct signaling cascades elicited by different formyl Peptide receptor 2 (FPR2) agonists. Int J Mol Sci, 14 (4): 7193-230. [PMID:23549262]

11. Chen K, Le Y, Liu Y, Gong W, Ying G, Huang J, Yoshimura T, Tessarollo L, Wang JM. (2010) A critical role for the g protein-coupled receptor mFPR2 in airway inflammation and immune responses. J Immunol, 184 (7): 3331-5. [PMID:20200280]

12. Chiang N, Fierro IM, Gronert K, Serhan CN. (2000) Activation of lipoxin A(4) receptors by aspirin-triggered lipoxins and select peptides evokes ligand-specific responses in inflammation. J Exp Med, 191 (7): 1197-208. [PMID:10748237]

13. Chiang N, Serhan CN, Dahlén SE, Drazen JM, Hay DW, Rovati GE, Shimizu T, Yokomizo T, Brink C. (2006) The lipoxin receptor ALX: potent ligand-specific and stereoselective actions in vivo. Pharmacol Rev, 58 (3): 463-87. [PMID:16968948]

14. Chiang N, Takano T, Arita M, Watanabe S, Serhan CN. (2003) A novel rat lipoxin A4 receptor that is conserved in structure and function. Br J Pharmacol, 139 (1): 89-98. [PMID:12746227]

15. Christophe T, Karlsson A, Dugave C, Rabiet MJ, Boulay F, Dahlgren C. (2001) The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan monocyte-expressed chemoattractant receptor FPRL2. J Biol Chem, 276 (24): 21585-93. [PMID:11285256]

16. Cilibrizzi A, Schepetkin IA, Bartolucci G, Crocetti L, Dal Piaz V, Giovannoni MP, Graziano A, Kirpotina LN, Quinn MT, Vergelli C. (2012) Synthesis, enantioresolution, and activity profile of chiral 6-methyl-2,4-disubstituted pyridazin-3(2H)-ones as potent N-formyl peptide receptor agonists. Bioorg Med Chem, 20 (12): 3781-92. [PMID:22607879]

17. Clish CB, O'Brien JA, Gronert K, Stahl GL, Petasis NA, Serhan CN. (1999) Local and systemic delivery of a stable aspirin-triggered lipoxin prevents neutrophil recruitment in vivo. Proc Natl Acad Sci USA, 96 (14): 8247-52. [PMID:10393980]

18. de Gaetano M, Butler E, Gahan K, Zanetti A, Marai M, Chen J, Cacace A, Hams E, Maingot C, McLoughlin A et al.. (2019) Asymmetric synthesis and biological evaluation of imidazole- and oxazole-containing synthetic lipoxin A4 mimetics (sLXms). Eur J Med Chem, 162: 80-108. [PMID:30419493]

19. De Yang, Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O. (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med, 192 (7): 1069-74. [PMID:11015447]

20. Deng X, Ueda H, Su SB, Gong W, Dunlop NM, Gao JL, Murphy PM, Wang JM. (1999) A synthetic peptide derived from human immunodeficiency virus type 1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R. Blood, 94 (4): 1165-73. [PMID:10438703]

21. Derian CK, Solomon HF, Higgins 3rd JD, Beblavy MJ, Santulli RJ, Bridger GJ, Pike MC, Kroon DJ, Fischman AJ. (1996) Selective inhibition of N-formylpeptide-induced neutrophil activation by carbamate-modified peptide analogues. Biochemistry, 35 (4): 1265-9. [PMID:8573582]

22. Devchand PR, Arita M, Hong S, Bannenberg G, Moussignac RL, Gronert K, Serhan CN. (2003) Human ALX receptor regulates neutrophil recruitment in transgenic mice: roles in inflammation and host defense. FASEB J, 17 (6): 652-9. [PMID:12665478]

23. Dufton N, Hannon R, Brancaleone V, Dalli J, Patel HB, Gray M, D'Acquisto F, Buckingham JC, Perretti M, Flower RJ. (2010) Anti-inflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation. J Immunol, 184 (5): 2611-9. [PMID:20107188]

24. Elagoz A, Henderson D, Babu PS, Salter S, Grahames C, Bowers L, Roy MO, Laplante P, Grazzini E, Ahmad S et al.. (2004) A truncated form of CKbeta8-1 is a potent agonist for human formyl peptide-receptor-like 1 receptor. Br J Pharmacol, 141 (1): 37-46. [PMID:14662730]

25. Filep JG, Zouki C, Petasis NA, Hachicha M, Serhan CN. (1999) Anti-inflammatory actions of lipoxin A(4) stable analogs are demonstrable in human whole blood: modulation of leukocyte adhesion molecules and inhibition of neutrophil-endothelial interactions. Blood, 94 (12): 4132-42. [PMID:10590058]

26. Fiore S, Maddox JF, Perez HD, Serhan CN. (1994) Identification of a human cDNA encoding a functional high affinity lipoxin A4 receptor. J Exp Med, 180 (1): 253-60. [PMID:8006586]

27. Fiore S, Romano M, Reardon EM, Serhan CN. (1993) Induction of functional lipoxin A4 receptors in HL-60 cells. Blood, 81 (12): 3395-403. [PMID:8389617]

28. Fiore S, Ryeom SW, Weller PF, Serhan CN. (1992) Lipoxin recognition sites. Specific binding of labeled lipoxin A4 with human neutrophils. J Biol Chem, 267 (23): 16168-76. [PMID:1322894]

29. Fiore S, Serhan CN. (1995) Lipoxin A4 receptor activation is distinct from that of the formyl peptide receptor in myeloid cells: inhibition of CD11/18 expression by lipoxin A4-lipoxin A4 receptor interaction. Biochemistry, 34 (51): 16678-86. [PMID:8527441]

30. Forsman H, Andréasson E, Karlsson J, Boulay F, Rabiet MJ, Dahlgren C. (2012) Structural characterization and inhibitory profile of formyl peptide receptor 2 selective peptides descending from a PIP2-binding domain of gelsolin. J Immunol, 189 (2): 629-37. [PMID:22706076]

31. Forsman H, Dahlgren C. (2009) Lipoxin A(4) metabolites/analogues from two commercial sources have no effects on TNF-alpha-mediated priming or activation through the neutrophil formyl peptide receptors. Scand J Immunol, 70 (4): 396-402. [PMID:19751275]

32. Freer RJ, Day AR, Muthukumaraswamy N, Pinon D, Wu A, Showell HJ, Becker EL. (1982) Formyl peptide chemoattractants: a model of the receptor on rabbit neutrophils. Biochemistry, 21 (2): 257-63. [PMID:6280748]

33. Fu H, Björkman L, Janmey P, Karlsson A, Karlsson J, Movitz C, Dahlgren C. (2004) The two neutrophil members of the formylpeptide receptor family activate the NADPH-oxidase through signals that differ in sensitivity to a gelsolin derived phosphoinositide-binding peptide. BMC Cell Biol, 5 (1): 50. [PMID:15625007]

34. Gao JL, Chen H, Filie JD, Kozak CA, Murphy PM. (1998) Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse. Genomics, 51 (2): 270-6. [PMID:9722950]

35. Gao JL, Guillabert A, Hu J, Le Y, Urizar E, Seligman E, Fang KJ, Yuan X, Imbault V, Communi D et al.. (2007) F2L, a peptide derived from heme-binding protein, chemoattracts mouse neutrophils by specifically activating Fpr2, the low-affinity N-formylpeptide receptor. J Immunol, 178 (3): 1450-6. [PMID:17237393]

36. Gavins FN, Yona S, Kamal AM, Flower RJ, Perretti M. (2003) Leukocyte antiadhesive actions of annexin 1: ALXR- and FPR-related anti-inflammatory mechanisms. Blood, 101 (10): 4140-7. [PMID:12560218]

37. Gewirtz AT, Collier-Hyams LS, Young AN, Kucharzik T, Guilford WJ, Parkinson JF, Williams IR, Neish AS, Madara JL. (2002) Lipoxin a4 analogs attenuate induction of intestinal epithelial proinflammatory gene expression and reduce the severity of dextran sodium sulfate-induced colitis. J Immunol, 168 (10): 5260-7. [PMID:11994483]

38. Godson C, Mitchell S, Harvey K, Petasis NA, Hogg N, Brady HR. (2000) Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol, 164 (4): 1663-7. [PMID:10657608]

39. Gronert K, Martinsson-Niskanen T, Ravasi S, Chiang N, Serhan CN. (2001) Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses. Am J Pathol, 158 (1): 3-9. [PMID:11141472]

40. Hanson J, Ferreirós N, Pirotte B, Geisslinger G, Offermanns S. (2013) Heterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A4. Biochem Pharmacol, 85 (12): 1795-802. [PMID:23643932]

41. Harada M, Habata Y, Hosoya M, Nishi K, Fujii R, Kobayashi M, Hinuma S. (2004) N-Formylated humanin activates both formyl peptide receptor-like 1 and 2. Biochem Biophys Res Commun, 324 (1): 255-61. [PMID:15465011]

42. Hayhoe RP, Kamal AM, Solito E, Flower RJ, Cooper D, Perretti M. (2006) Annexin 1 and its bioactive peptide inhibit neutrophil-endothelium interactions under flow: indication of distinct receptor involvement. Blood, 107 (5): 2123-30. [PMID:16278303]

43. He HQ, Liao D, Wang ZG, Wang ZL, Zhou HC, Wang MW, Ye RD. (2013) Functional characterization of three mouse formyl peptide receptors. Mol Pharmacol, 83 (2): 389-98. [PMID:23160941]

44. He R, Sang H, Ye RD. (2003) Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R. Blood, 101 (4): 1572-81. [PMID:12393391]

45. He R, Tan L, Browning DD, Wang JM, Ye RD. (2000) The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met is a potent chemotactic agonist for mouse formyl peptide receptor. J Immunol, 165 (8): 4598-605. [PMID:11035102]

46. Hecht I, Rong J, Sampaio AL, Hermesh C, Rutledge C, Shemesh R, Toporik A, Beiman M, Dassa L, Niv H et al.. (2009) A novel peptide agonist of formyl-peptide receptor-like 1 (ALX) displays anti-inflammatory and cardioprotective effects. J Pharmacol Exp Ther, 328 (2): 426-34. [PMID:19023040]

47. Hu JY, Le Y, Gong W, Dunlop NM, Gao JL, Murphy PM, Wang JM. (2001) Synthetic peptide MMK-1 is a highly specific chemotactic agonist for leukocyte FPRL1. J Leukoc Biol, 70 (1): 155-61. [PMID:11435499]

48. Jiang H, Kuang Y, Wu Y, Smrcka A, Simon MI, Wu D. (1996) Pertussis toxin-sensitive activation of phospholipase C by the C5a and fMet-Leu-Phe receptors. J Biol Chem, 271 (23): 13430-4. [PMID:8662841]

49. Kim HJ, Cho SH, Park JS, Lee TH, Lee EJ, Kim YH, Uh ST, Chung IY, Kim MK, Choi IS et al.. (2012) Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and aspirin exacerbated respiratory diseases. J Hum Genet, 57 (4): 247-53. [PMID:22377711]

50. Kirpotina LN, Khlebnikov AI, Schepetkin IA, Ye RD, Rabiet MJ, Jutila MA, Quinn MT. (2010) Identification of novel small-molecule agonists for human formyl peptide receptors and pharmacophore models of their recognition. Mol Pharmacol, 77 (2): 159-70. [PMID:19903830]

51. Klein C, Paul JI, Sauvé K, Schmidt MM, Arcangeli L, Ransom J, Trueheart J, Manfredi JP, Broach JR, Murphy AJ. (1998) Identification of surrogate agonists for the human FPRL-1 receptor by autocrine selection in yeast. Nat Biotechnol, 16 (13): 1334-7. [PMID:9853614]

52. Kretschmer D, Gleske AK, Rautenberg M, Wang R, Köberle M, Bohn E, Schöneberg T, Rabiet MJ, Boulay F, Klebanoff SJ et al.. (2010) Human formyl peptide receptor 2 senses highly pathogenic Staphylococcus aureus. Cell Host Microbe, 7 (6): 463-73. [PMID:20542250]

53. Krishnamoorthy S, Recchiuti A, Chiang N, Fredman G, Serhan CN. (2012) Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs. Am J Pathol, 180 (5): 2018-27. [PMID:22449948]

54. Krishnamoorthy S, Recchiuti A, Chiang N, Yacoubian S, Lee CH, Yang R, Petasis NA, Serhan CN. (2010) Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proc Natl Acad Sci USA, 107 (4): 1660-5. [PMID:20080636]

55. Kucharzik T, Gewirtz AT, Merlin D, Madara JL, Williams IR. (2003) Lateral membrane LXA4 receptors mediate LXA4's anti-inflammatory actions on intestinal epithelium. Am J Physiol, Cell Physiol, 284 (4): C888-96. [PMID:12456400]

56. Kurosaka K, Chen Q, Yarovinsky F, Oppenheim JJ, Yang D. (2005) Mouse cathelin-related antimicrobial peptide chemoattracts leukocytes using formyl peptide receptor-like 1/mouse formyl peptide receptor-like 2 as the receptor and acts as an immune adjuvant. J Immunol, 174 (10): 6257-65. [PMID:15879124]

57. Lad PM, Olson CV, Smiley PA. (1985) Association of the N-formyl-Met-Leu-Phe receptor in human neutrophils with a GTP-binding protein sensitive to pertussis toxin. Proc Natl Acad Sci USA, 82 (3): 869-73. [PMID:2983319]

58. Le Y, Gong W, Li B, Dunlop NM, Shen W, Su SB, Ye RD, Wang JM. (1999) Utilization of two seven-transmembrane, G protein-coupled receptors, formyl peptide receptor-like 1 and formyl peptide receptor, by the synthetic hexapeptide WKYMVm for human phagocyte activation. J Immunol, 163 (12): 6777-84. [PMID:10586077]

59. Le Y, Gong W, Tiffany HL, Tumanov A, Nedospasov S, Shen W, Dunlop NM, Gao JL, Murphy PM, Oppenheim JJ et al.. (2001) Amyloid (beta)42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1. J Neurosci, 21 (2): RC123. [PMID:11160457]

60. Le Y, Jiang S, Hu J, Gong W, Su S, Dunlop NM, Shen W, Li B, Ming Wang J. (2000) N36, a synthetic N-terminal heptad repeat domain of the HIV-1 envelope protein gp41, is an activator of human phagocytes. Clin Immunol, 96 (3): 236-42. [PMID:10964542]

61. Lee HY, Kim MK, Park KS, Bae YH, Yun J, Park JI, Kwak JY, Bae YS. (2005) Serum amyloid A stimulates matrix-metalloproteinase-9 upregulation via formyl peptide receptor like-1-mediated signaling in human monocytic cells. Biochem Biophys Res Commun, 330 (3): 989-98. [PMID:15809093]

62. Levy BD, Fokin VV, Clark JM, Wakelam MJ, Petasis NA, Serhan CN. (1999) Polyisoprenyl phosphate (PIPP) signaling regulates phospholipase D activity: a 'stop' signaling switch for aspirin-triggered lipoxin A4. FASEB J, 13 (8): 903-11. [PMID:10224233]

63. Liu M, Chen K, Yoshimura T, Liu Y, Gong W, Wang A, Gao JL, Murphy PM, Wang JM. (2012) Formylpeptide receptors are critical for rapid neutrophil mobilization in host defense against Listeria monocytogenes. Sci Rep, 2: 786. [PMID:23139859]

64. Maddox JF, Hachicha M, Takano T, Petasis NA, Fokin VV, Serhan CN. (1997) Lipoxin A4 stable analogs are potent mimetics that stimulate human monocytes and THP-1 cells via a G-protein-linked lipoxin A4 receptor. J Biol Chem, 272 (11): 6972-8. [PMID:9054386]

65. Maddox JF, Serhan CN. (1996) Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion: selective inactivation by dehydrogenation and reduction. J Exp Med, 183 (1): 137-46. [PMID:8551217]

66. Miao Z, Premack BA, Wei Z, Wang Y, Gerard C, Showell H, Howard M, Schall TJ, Berahovich R. (2007) Proinflammatory proteases liberate a discrete high-affinity functional FPRL1 (CCR12) ligand from CCL23. J Immunol, 178 (11): 7395-404. [PMID:17513790]

67. Migeotte I, Communi D, Parmentier M. (2006) Formyl peptide receptors: a promiscuous subfamily of G protein-coupled receptors controlling immune responses. Cytokine Growth Factor Rev, 17 (6): 501-19. [PMID:17084101]

68. Morley AD, King S, Roberts B, Lever S, Teobald B, Fisher A, Cook T, Parker B, Wenlock M, Phillips C et al.. (2012) Lead optimisation of pyrazoles as novel FPR1 antagonists. Bioorg Med Chem Lett, 22 (1): 532-6. [PMID:22094028]

69. Murphy PM, Ozçelik T, Kenney RT, Tiffany HL, McDermott D, Francke U. (1992) A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family. J Biol Chem, 267 (11): 7637-43. [PMID:1373134]

70. Nanamori M, Cheng X, Mei J, Sang H, Xuan Y, Zhou C, Wang MW, Ye RD. (2004) A novel nonpeptide ligand for formyl peptide receptor-like 1. Mol Pharmacol, 66 (5): 1213-22. [PMID:15308762]

71. NCBI. LPHN2 - Ovarian cancer and depression. Accessed on 02/05/2013. Modified on 02/05/2013. NCBI Geoprofiles, http://www.ncbi.nlm.nih.gov/geoprofiles

72. Norling LV, Dalli J, Flower RJ, Serhan CN, Perretti M. (2012) Resolvin D1 limits polymorphonuclear leukocyte recruitment to inflammatory loci: receptor-dependent actions. Arterioscler Thromb Vasc Biol, 32 (8): 1970-8. [PMID:22499990]

73. Partida-Sánchez S, Cockayne DA, Monard S, Jacobson EL, Oppenheimer N, Garvy B, Kusser K, Goodrich S, Howard M, Harmsen A et al.. (2001) Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat Med, 7 (11): 1209-16. [PMID:11689885]

74. Partidá-Sánchez S, Rivero-Nava L, Shi G, Lund FE. (2007) CD38: an ecto-enzyme at the crossroads of innate and adaptive immune responses. Adv Exp Med Biol, 590: 171-83. [PMID:17191385]

75. Perretti M, Chiang N, La M, Fierro IM, Marullo S, Getting SJ, Solito E, Serhan CN. (2002) Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Nat Med, 8 (11): 1296-302. [PMID:12368905]

76. Petri MH, Laguna-Fernandez A, Tseng CN, Hedin U, Perretti M, Bäck M. (2015) Aspirin-triggered 15-epi-lipoxin A₄ signals through FPR2/ALX in vascular smooth muscle cells and protects against intimal hyperplasia after carotid ligation. Int J Cardiol, 179: 370-2. [PMID:25464488]

77. Pinilla C, Edwards BS, Appel JR, Yates-Gibbins T, Giulianotti MA, Medina-Franco JL, Young SM, Santos RG, Sklar LA, Houghten RA. (2013) Selective agonists and antagonists of formylpeptide receptors: duplex flow cytometry and mixture-based positional scanning libraries. Mol Pharmacol, 84 (3): 314-24. [PMID:23788657]

78. Planagumà A, Domenech T, Jover I, Ramos I, Sentellas S, Malhotra R, Miralpeix M. (2013) Lack of activity of 15-epi-lipoxin A4 on FPR2/ALX and CysLT1 receptors in interleukin-8-driven human neutrophil function. Clin Exp Immunol, 173 (2): 298-309. [PMID:23607720]

79. Prat C, Bestebroer J, de Haas CJ, van Strijp JA, van Kessel KP. (2006) A new staphylococcal anti-inflammatory protein that antagonizes the formyl peptide receptor-like 1. J Immunol, 177 (11): 8017-26. [PMID:17114475]

80. Qiu FH, Devchand PR, Wada K, Serhan CN. (2001) Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils. FASEB J, 15 (14): 2736-8. [PMID:11687510]

81. Quehenberger O, Prossnitz ER, Cavanagh SL, Cochrane CG, Ye RD. (1993) Multiple domains of the N-formyl peptide receptor are required for high-affinity ligand binding. Construction and analysis of chimeric N-formyl peptide receptors. J Biol Chem, 268 (24): 18167-75. [PMID:8349692]

82. Rabiet MJ, Huet E, Boulay F. (2005) Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR. Eur J Immunol, 35 (8): 2486-95. [PMID:16025565]

83. Resnati M, Pallavicini I, Wang JM, Oppenheim J, Serhan CN, Romano M, Blasi F. (2002) The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R. Proc Natl Acad Sci USA, 99 (3): 1359-64. [PMID:11818541]

84. Sawmynaden P, Perretti M. (2006) Glucocorticoid upregulation of the annexin-A1 receptor in leukocytes. Biochem Biophys Res Commun, 349 (4): 1351-5. [PMID:16973129]

85. Seo JK, Choi SY, Kim Y, Baek SH, Kim KT, Chae CB, Lambeth JD, Suh PG, Ryu SH. (1997) A peptide with unique receptor specificity: stimulation of phosphoinositide hydrolysis and induction of superoxide generation in human neutrophils. J Immunol, 158 (4): 1895-901. [PMID:9029131]

86. Shen W, Proost P, Li B, Gong W, Le Y, Sargeant R, Murphy PM, Van Damme J, Wang JM. (2000) Activation of the chemotactic peptide receptor FPRL1 in monocytes phosphorylates the chemokine receptor CCR5 and attenuates cell responses to selected chemokines. Biochem Biophys Res Commun, 272 (1): 276-83. [PMID:10872839]

87. Simiele F, Recchiuti A, Mattoscio D, De Luca A, Cianci E, Franchi S, Gatta V, Parolari A, Werba JP, Camera M et al.. (2012) Transcriptional regulation of the human FPR2/ALX gene: evidence of a heritable genetic variant that impairs promoter activity. FASEB J, 26 (3): 1323-33. [PMID:22131270]

88. Sodin-Semrl S, Spagnolo A, Barbaro B, Varga J, Fiore S. (2004) Lipoxin A4 counteracts synergistic activation of human fibroblast-like synoviocytes. Int J Immunopathol Pharmacol, 17 (1): 15-25. [PMID:15000862]

89. Sodin-Semrl S, Spagnolo A, Mikus R, Barbaro B, Varga J, Fiore S. (2004) Opposing regulation of interleukin-8 and NF-kappaB responses by lipoxin A4 and serum amyloid A via the common lipoxin A receptor. Int J Immunopathol Pharmacol, 17 (2): 145-56. [PMID:15171815]

90. Sodin-Semrl S, Taddeo B, Tseng D, Varga J, Fiore S. (2000) Lipoxin A4 inhibits IL-1 beta-induced IL-6, IL-8, and matrix metalloproteinase-3 production in human synovial fibroblasts and enhances synthesis of tissue inhibitors of metalloproteinases. J Immunol, 164 (5): 2660-6. [PMID:10679106]

91. Southgate EL, He RL, Gao JL, Murphy PM, Nanamori M, Ye RD. (2008) Identification of formyl peptides from Listeria monocytogenes and Staphylococcus aureus as potent chemoattractants for mouse neutrophils. J Immunol, 181 (2): 1429-37. [PMID:18606697]

92. Stalder AK, Lott D, Strasser DS, Cruz HG, Krause A, Groenen PM, Dingemanse J. (2017) Biomarker-guided clinical development of the first-in-class anti-inflammatory FPR2/ALX agonist ACT-389949. Br J Clin Pharmacol, 83 (3): 476-486. [PMID:27730665]

93. Stenfeldt AL, Karlsson J, Wennerås C, Bylund J, Fu H, Dahlgren C. (2007) Cyclosporin H, Boc-MLF and Boc-FLFLF are antagonists that preferentially inhibit activity triggered through the formyl peptide receptor. Inflammation, 30 (6): 224-9. [PMID:17687636]

94. Su SB, Gao Jl, Gong Wh, Dunlop NM, Murphy PM, Oppenheim JJ, Wang JM. (1999) T21/DP107, A synthetic leucine zipper-like domain of the HIV-1 envelope gp41, attracts and activates human phagocytes by using G-protein-coupled formyl peptide receptors. J Immunol, 162 (10): 5924-30. [PMID:10229829]

95. Su SB, Gong W, Gao JL, Shen W, Murphy PM, Oppenheim JJ, Wang JM. (1999) A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells. J Exp Med, 189 (2): 395-402. [PMID:9892621]

96. Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN. (1997) Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med, 185 (9): 1693-704. [PMID:9151906]

97. Tiffany HL, Lavigne MC, Cui YH, Wang JM, Leto TL, Gao JL, Murphy PM. (2001) Amyloid-beta induces chemotaxis and oxidant stress by acting at formylpeptide receptor 2, a G protein-coupled receptor expressed in phagocytes and brain. J Biol Chem, 276 (26): 23645-52. [PMID:11316806]

98. Waechter V, Marti-Jaun J, Weber A, Madi ZL, Hersberger M. (2012) No evidence for the involvement of the lipoxin A4 receptor (FPR2/ALX ) gene in the susceptibility to coronary artery disease. Clin Chem Lab Med, 50 (1): 177-9. [PMID:22734147]

99. Walther A, Riehemann K, Gerke V. (2000) A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR. Mol Cell, 5 (5): 831-40. [PMID:10882119]

100. Wang CS, Baker OJ. (2018) The G-Protein-Coupled Receptor ALX/Fpr2 Regulates Adaptive Immune Responses in Mouse Submandibular Glands. Am J Pathol, 188 (7): 1555-1562. [PMID:29684359]

101. Yang EM, Kim SH, Kim NH, Park HS. (2010) The genetic association of the FPRL1 promoter polymorphism with chronic urticaria in a Korean population. Ann Allergy Asthma Immunol, 105 (1): 96-7. [PMID:20642210]

102. Ye RD, Boulay F, Wang JM, Dahlgren C, Gerard C, Parmentier M, Serhan CN, Murphy PM. (2009) International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacol Rev, 61 (2): 119-61. [PMID:19498085]

103. Ying G, Iribarren P, Zhou Y, Gong W, Zhang N, Yu ZX, Le Y, Cui Y, Wang JM. (2004) Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. J Immunol, 172 (11): 7078-85. [PMID:15153530]

104. Zhou C, Zhang S, Nanamori M, Zhang Y, Liu Q, Li N, Sun M, Tian J, Ye PP, Cheng N et al.. (2007) Pharmacological characterization of a novel nonpeptide antagonist for formyl peptide receptor-like 1. Mol Pharmacol, 72 (4): 976-83. [PMID:17652444]

Contributors

Show »

How to cite this page

Magnus Bäck, Nan Chiang, Sven-Erik Dahlén, Jeffrey Drazen, Jilly F. Evans, G. Enrico Rovati, Charles N. Serhan, Takao Shimizu, Takehiko Yokomizo.
Formylpeptide receptors: FPR2/ALX. Last modified on 30/06/2022. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=223.