Heterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A4

Lipoxin A(4) (LXA(4)) has been described as an anti-inflammatory mediator, which exerts its effects through the formyl peptide receptor FPR2, also known as ALX. However, there has been a controversy whether or not cells expressing FPR2/ALX, such as neutrophils, respond to LXA(4). We, therefore, systematically examined the ability of the human and murine forms of the receptor to respond to LXA(4). We show that both receptor orthologues responded to the FPR2/ALX peptide agonist WKYMVM when expressed heterologously. In contrast, LXA(4) from different sources neither increased [Ca2+](i) and extracellular-signal-regulated kinase (ERIC) phosphorylation, nor did it induce a decrease in cAMP levels or a translocation of beta-arrestin. Also, several LXA(4) analogs were found to be unable to signal through FPR2/ALX. We conclude that FPR2/ALX is not activated by LXA(4) and that the molecular mechanism by which LXA(4) functions still needs to be identified. (C) 2013 Elsevier Inc. All rights reserved.