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

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• 作者：Julien Hanson^a ; ^b ; ^d ; ^{j.hanson@ulg.ac.be} ; Nerea Ferreiró ; s^c ; ^{FerreirosBouzas@em.uni-frankfurt.de} ; Bernard Pirotte^d ; ^{b.pirotte@ulg.ac.be} ; Gerd Geisslinger^c ; ^{geisslinger@em.uni-frankfurt.de} ; Stefan Offermanns^a ; ^e ; ^{Stefan.Offermanns@mpi-bn.mpg.de}
• 关键词：Lipoxin ; ALX ; FPR2 ; Formyl peptide receptor ; Resolution of inflammation
• 刊名：Biochemical Pharmacology
• 出版年：2013
• 出版时间：15 June, 2013
• 年：2013
• 卷：85
• 期：12
• 页码：1795-1802
• 全文大小：1134 K

文摘

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 ¦Â-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.