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

Julien Hanson, Nerea Ferreirós, Bernard Pirotte, Gerd Geisslinger, Stefan Offermanns

Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany. j.hanson@ulg.ac.be

Biochemical pharmacology 2013 Jun 15

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Lipoxin A₄ (LXA₄) 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 LXA₄. We, therefore, systematically examined the ability of the human and murine forms of the receptor to respond to LXA₄. We show that both receptor orthologues responded to the FPR2/ALX peptide agonist WKYMVM when expressed heterologously. In contrast, LXA₄ from different sources neither increased [Ca²⁺](i) and extracellular-signal-regulated kinase (ERK) phosphorylation, nor did it induce a decrease in cAMP levels or a translocation of β-arrestin. Also, several LXA₄ analogs were found to be unable to signal through FPR2/ALX. We conclude that FPR2/ALX is not activated by LXA₄ and that the molecular mechanism by which LXA₄ functions still needs to be identified. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Julien Hanson, Nerea Ferreirós, Bernard Pirotte, Gerd Geisslinger, Stefan Offermanns. Heterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A₄. Biochemical pharmacology. 2013 Jun 15;85(12):1795-802