Department of Pharmacology, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany.
Biochem Pharmacol. 2013 Jun 15;85(12):1795-802. doi: 10.1016/j.bcp.2013.04.019. Epub 2013 May 1.
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⁺ 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.
脂氧素 A₄（LXA₄）被描述为一种抗炎介质，通过形式肽受体 FPR2（也称为 ALX）发挥作用。然而，关于表达 FPR2/ALX 的细胞（如中性粒细胞）是否对 LXA₄作出反应一直存在争议。因此，我们系统地检查了受体的人源和鼠源形式对 LXA₄的反应能力。我们发现，两种受体同源物在异源表达时均对 FPR2/ALX 肽激动剂 WKYMVM 作出反应。相比之下，不同来源的 LXA₄既不能增加 Ca²⁺ 和细胞外信号调节激酶（ERK）磷酸化，也不能降低 cAMP 水平或β-arrestin 的易位。此外，还发现几种 LXA₄类似物不能通过 FPR2/ALX 发出信号。我们得出结论，FPR2/ALX 不能被 LXA₄激活，LXA₄ 发挥作用的分子机制仍有待确定。
