Interactions of lysophospholipids and mast cells

Abstract

PHOSPHOLIPID and protein are the major components of biological membranes, and much is known about their organisation in various cell membranes^1,2. An important question concerns the existence and significance of specific protein–phospholipid interactions in membranes. Among the methods used to elucidate these interactions is the study of the regulatory function of specific phospholipids in intact cells. Phosphatidylserine (PS) enhances the secretory response of the mast cell³ in a highly specific manner. Other diacyl phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol, phosphatidylinositol and phosphatidic acid, are ineffective^3–5 and several N-substituted derivatives of PS are competitive inhibitors of the effect of PS on mast cells⁶. Furthermore, PS selectively enhances the response of cells to IgE-dependent secretagogues^7,8 without increasing the response of the cells to IgE-independent agents such as polymyxin B⁹, chymotrypsin³, compound 48/80 (refs 3, 9), or A23187 (D. L. and T. W. M., unpublished). As histamine secretion involves a major alteration in the organisation of membrane components¹⁰, the effect of PS on secretion makes it possible to study a complex membrane event with an established phospholipid specificity. Previously, we have used PS of various fatty acid compositions¹¹: dimyristoyl PS, dipalmitoyl PS, and distearoyl PS. We now provide evidence that lysophosphatidyl-serine (lyso-PS) generated from bovine brain PS by the action of phospholipase A₂ activates mast cell secretion induced by concanavalin A (Con A) at 1/30th to 1/50th the concentration of PS required for an equivalent response. Although some characteristics of the activation of mast cell secretion by lyso-PS resemble those observed with PS, its mode of interaction with the cell may be different; PS acts on mast cells in a micellar state¹², but lyso-PS acts to potentiate secretion well below its critical micelle concentration (CMC).