The FPR2/ALX receptor is a member of the formyl peptide receptor (FPR) superfamily which in humans also includes formyl peptide receptor 1 (FPR1) and formyl peptide receptor 3 (FPR3). Recent interest in this specific receptor reflects its intriguing anti-inflammatory and proresolving bioactions in contrast to other FPR family members (Serhan 2007; Maderna et al. 2010). FPR2/ALX was identified as a specific receptor for lipoxin A4 (LXA4) in 1992 (Fiore et al. 1992). Using radiolabeled [11,12-3H]LXA4 and human polymorphonuclear leukocytes (PMNs) in which LXA4-mediated action had previously been identified, specific stereoselective binding with a Kd of approximately 0.5 nM was demonstrated. Modulation of [11,12-3H]LXA4binding by guanosine analogs indicated that this binding site was a G-protein-coupled receptor...
The authors thank Dr. Aisling Kennedy and Dr. Eoin Brennan for their helpful comments. Work in the authors’ lab is funded by Science Foundation Ireland, The Health Research Board, and The Government of Ireland Programme for Research in Third-Level Institutions. Karen Nolan is an IRCSET postgraduate Scholar.
- Brancaleone V, Dalli J, Bena S, Flower RJ, Cirino G, Perretti M. Evidence for an anti-inflammatory loop centered on polymorphonuclear leukocyte formyl peptide receptor 2/lipoxin A4 receptor and operative in the inflamed microvasculature. J Immunol. 2011;186:4905–14.PubMedPubMedCentralCrossRefGoogle Scholar
- Dufton N, Hannon R, Brancaleone V, Dalli J, Patel HB, Gray M, D’Acquisto F, Buckingham JC, Perretti M, Flower RJ. Anti-inflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation. J Immunol. 2010;184:2611–9.PubMedPubMedCentralCrossRefGoogle Scholar
- Guilford WJ, Bauman JG, Skuballa W, Bauer S, Wei GP, Davey D, Schaefer C, Mallari C, Terkelsen J, Tseng JL, Shen J, Subramanyam B, Schottelius AJ, Parkinson JF. Novel 3-oxa lipoxin A4 analogues with enhanced chemical and metabolic stability have anti-inflammatory activity in vivo. J Med Chem. 2004;47(8):2157–65.PubMedPubMedCentralCrossRefGoogle Scholar
- Hecht I, Rong J, Sampaio AL, Hermesh C, Rutledge C, Shemesh R, Toporik A, Beiman M, Dassa L, Niv H, Cojocaru G, Zauberman A, Rotman G, Perretti M, Vinten-Johansen J, Cohen Y. A novel peptide agonist of formyl-peptide receptor-like 1 (ALX) displays anti-inflammatory and cardioprotective effects. J Pharmacol Exp Ther. 2009;328:426–34.PubMedPubMedCentralCrossRefGoogle Scholar
- Leonard MO, Hannan K, Burne MJ, Lappin DW, Doran P, Coleman P, Stenson C, Taylor CT, Daniels F, Godson C, Petasis NA, Rabb H, Brady HR. 15-Epi-16-(para-fluorophenoxy)-lipoxin A(4)-methyl ester, a synthetic analogue of 15-epi-lipoxin A(4), is protective in experimental ischemic acute renal failure. J Am Soc Nephrol. 2002;13:1657–62.PubMedPubMedCentralCrossRefGoogle Scholar
- Martins V, Valenca SS, Farias-Filho FA, Molinaro R, Simoes RL, Ferreira TP, Silva PM, Hogaboam CM, Kunkel SL, Fierro IM, Canetti C, Benjamim CF. ATLa, an aspirin-triggered lipoxin A4 synthetic analog, prevents the inflammatory and fibrotic effects of bleomycin-induced pulmonary fibrosis. J Immunol. 2009;182:5374–81.PubMedPubMedCentralCrossRefGoogle Scholar
- Mitchell S, Thomas G, Harvey K, Cottell D, Reville K, Berlasconi G, Petasis NA, Erwig L, Rees AJ, Savill J, Brady HR, Godson C. Lipoxins, aspirin-triggered epi-lipoxins, lipoxin stable analogues, and the resolution of inflammation: stimulation of macrophage phagocytosis of apoptotic neutrophils in vivo. J Am Soc Nephrol. 2002;13(10):2497–507.PubMedPubMedCentralCrossRefGoogle Scholar