title: Heterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A₄.
abstract: 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.
authors: Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany. j.hanson@ulg.ac.be
authors: Julien
authors: J
authors: Hanson
authors: Nerea
authors: N
authors: Ferreirós
authors: Bernard
authors: B
authors: Pirotte
authors: Gerd
authors: G
authors: Geisslinger
authors: Stefan
authors: S
authors: Offermanns
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D044045:Lipoxins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D044042:Receptors, Formyl Peptide / Q000008:administration & dosage* / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D044067:Receptors, Lipoxin / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C105101:FPR2 protein, human; C469988:Fpr1 protein, mouse; C509871:HSH2 protein, mouse; D044045:Lipoxins; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C040527:lipoxin A4; D000242:Cyclic AMP