Signalling mechanism in the lysophosphatidylserine-induced activation of mouse mast cells

Abstract

Lysophosphatidylserine (0.1–1 μM) elicits histamine release in isolated mouse peritoneal mast cells. The effect becomes manifest after a lag of 30 s and reaches completion in 5 min. Maximal activity is observed when serine is in l-configuration. As shown by the activity of a lysophosphatidylserine analogue lacking the OH group in C 2 position of glycerol, conversion into phosphatidylserine is not required. When 32PO 4-labeled mast cells are challenged 2–5 min with lysophosphatidylserine, the labeling of phosphatidate, phosphatidylinositol and phosphatidylcholine is increased. When [ 3H]arachidonate-labeled mast cells are used, lysophosphatidylserine increases the appearance of isotopic diacylglycerol and phosphatidate. Like the secretory response, these effects are independent of the presence of extracellular Ca 2+. Incubations in the presence of [ 3H]glycerol show that lysophosphatidylserine does not activate the de novo synthesis of phospholipids. In agreement with a participation of phosphoinositidase C in the action of lysophosphatidylserine, we observe accumulation of inositol phosphates in [ 3H]inositol labeled mast cells incubated in the presence of Li +. The results suggest that lysophosphatidylserine delivers its stimulus to mast cells, by the activation of phosphoinositide-dependent signalling mechanism.