Fourcade O, Simon M F, Viodé C, Rugani N, Leballe F, Ragab A, Fournié B, Sarda L, Chap H
Institut National de la Santé et de la Recherche Médicale, Unité 326, Phospholipides Membranaires, Signalisation Cellulaire et Lipoprotéines, Hôpital Purpan, Toulouse, France.
Cell. 1995 Mar 24;80(6):919-27. doi: 10.1016/0092-8674(95)90295-3.
Nonpancreatic secretory phospholipase A2 (sPLA2) displays proinflammatory properties; however, its physiological substrate is not identified. Although inactive toward intact cells, sPLA2 hydrolyzed phospholipids in membrane microvesicles shed from Ca(2+)-loaded erythrocytes as well as from platelets and from whole blood cells challenged with inflammatory stimuli. sPLA2 was stimulated upon degradation of sphingomyelin (SPH) and produced lysophosphatidic acid (LPA), which induced platelet aggregation. Finally, lysophospholipid-containing vesicles and sPLA2 were detected in inflammatory fluids in relative proportions identical to those used in vitro. We conclude that upon loss of phospholipid asymmetry, cell-derived microvesicles provide a preferential substrate for sPLA2. SPH hydrolysis, which is provoked by various cytokines, regulates sPLA2 activity, and the novel lipid mediator LPA can be generated by this pathway.
非胰腺分泌型磷脂酶A2（sPLA2）具有促炎特性；然而，其生理底物尚未明确。尽管sPLA2对完整细胞无活性，但它能水解从钙离子负载的红细胞、血小板以及受到炎症刺激的全血细胞脱落的膜微泡中的磷脂。鞘磷脂（SPH）降解时sPLA2被激活，并产生溶血磷脂酸（LPA），后者可诱导血小板聚集。最后，在炎性液体中检测到含溶血磷脂的囊泡和sPLA2，其相对比例与体外实验所用的相同。我们得出结论，磷脂不对称性丧失时，细胞衍生的微泡为sPLA2提供了优先底物。由多种细胞因子引发的SPH水解调节sPLA2活性，并且这条途径可生成新的脂质介质LPA。
