Induction of neutrophil calcium mobilization by phosphatidic acid-enrichedplasma membranes

The purpose of this investigation was to determine if phosphatidic acid (PA ) confined to biological membranes could induce physiological responses sim ilar to those induced by exogenous PA. Plasma membranes were treated with p hospholipase D (PLD) to increase concentrations of PA within the membranes. Membranes were also treated with other phospholipases including phospholip ase A(2) (PLA(2)), and phospholipase C (PLC), which degrade phospholipids w ithout generating PA. A phosphatidylinositol (PI) 3'-kinase inhibitor, LY29 4002, strongly and selectively inhibited intracellular calcium mobilization induced by PLD-treated membranes. This study suggests that PA-enriched pla sma membranes, which exert their effects by activating a unique signaling p athway mediated by PI 3'-kinase, are potent, physiologically relevant initi ators of neutrophil activation.