Activation of PAF receptors results in enhanced synthesis of 2-arachidonoylglycerol (2-AG) in immune cells
Activation of PAF receptors results in enhanced synthesis of 2-arachidonoylglycerol (2-AG) in immune cells
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DOI：
10.1096/fj.01-0181com
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发表时间：
2001-10-01
期刊：
影响因子：
4.8
通讯作者：
Schmid, HHO
中科院分区：
文献类型：
--
作者：
Berdyshev, EV;Schmid, PC;Schmid, HHO
内源性大麻素信号系统被认为在细胞功能的控制中起下调作用。然而，激活内源性大麻素合成的因素知之甚少，两种已知内源性大麻素，2-花生四烯醇甘油（2-AG）或n-花生四烯醇乙醇胺（20:4n-6 NAE, anandamide），哪一种具有生理重要性。我们通过研究血小板活化因子（PAF）与人类血小板和小鼠P388D1巨噬细胞中2-AG和anandamide的生成之间的可能联系来解决这些问题。人血小板对刺激作出反应，产生各种1-和2-单酰基甘油，包括2-AG，而P388D1巨噬细胞的刺激诱导了2-AG的快速和选择性生成，并立即释放到培养基中。PAF的作用是受体介导的，PAF受体拮抗剂BN52021阻断了这一作用。治疗没有改变巨噬细胞或富血小板血浆中anandamide的含量。PI-和pc特异性磷脂酶C （U73122和D609）抑制剂以及pi3激酶抑制剂（wortmannin）可减弱paf诱导的巨噬细胞2-AG的产生。这些数据提示内源性大麻素系统在控制免疫细胞激活状态中的直接作用，并表明2-AG而不是anandamide是内源性大麻素在免疫细胞促炎刺激反应中迅速产生的。
The endocannabinoid signaling system is believed to play a down-regulatory role in the control of cell functions. However, little is known about the factors activating endocannabinoid synthesis and which of two known endocannabinoids, 2-arachidonoylglycerol (2-AG) or N-arachidonoylethanolamine (20:4n-6 NAE, anandamide), is of physiological importance. We approached these questions by studying a possible link between cell activation with 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor, PAF) and the generation of 2-AG and anandamide in human platelets and mouse P388D1 macrophages. Human platelets responded to stimulation with the production of various 1- and 2-monoacylglycerols, including 2-AG, whereas stimulation of P388D1 macrophages induced the rapid and selective generation of 2-AG, which was immediately released into the medium. The effect of PAF was receptor mediated, as PAF receptor antagonist BN52021 blocked the effect. The treatment did not change the content of anandamide in either macrophages or platelet-rich plasma. The inhibitors of PI- and PC-specific phospholipases C (U73122 and D609) as well as PI3-kinase inhibitor (wortmannin) attenuated PAF-induced 2-AG production in macrophages. These data suggest a direct role for the endocannabinoid system in controlling immune cell activation status and indicate that 2-AG rather than anandamide is the endocannabinoid rapidly produced in response to proinflammatory stimulation of immune cells.