CA2-RELEASE INDUCED BY LYSOPHOSPHATIDYLSERINE IN MAST-CELLS( INFLUX, PHOSPHOINOSITIDE HYDROLYSIS, AND HISTAMINE)

We have previously demonstrated that snake venom phospholipases A(2) ( PLA(2)s) and mammalian PLA(2)s induced inflammatory processes. This ef fect was correlated with the activity of the enzymes and the release o f lipid mediators. We have now determined the role of lysophosphatidyl serine (LysoPS) as an inflammatory lipid mediator. Thus, we have studi ed the possibility that intracellular calcium concentration, phosphoin ositide hydrolysis, and the subsequent histamine release in mast cells is due to the action of lysophosphatidylserine. Lysophosphatidylserin e-stimulated release of histamine was significantly higher than releas e by other lysophospholipids. The contribution of increased phospholip ase C activity and the intracellular Ca2+ influx were therefore examin ed. LysoPS increased mast cell calcium concentration, and this increme nt was associated with phospholipase C activation and release of inosi tol phosphates. The increase in intracellular calcium and histamine de granulation induced by LysoPS were inhibited by apomorphine. Pretreatm ent of mast cells with pertussis toxin decreased the secretagogic effe ct of LysoPS and compound 48/80 without modifying the effect of the io nophore A23187. These results suggest that pertussis toxin-sensitive C -protein might be involved in the mast cell degranulation produced by lysophosphatidylserine and allow the increase in phospholipase C activ ity, thus enhancing intracellular calcium concentration, which then in duces exocytosis of histamine. (C) 1995 Wiley-Liss, Inc.