Induction of neutrophil calcium mobilization by phosphatidic acid-enriched plasma membranes.
The purpose of this investigation was to determine if phosphatidic acid (PA) confined to biological membranes could induce physiological responses similar to those induced by exogenous PA. Plasma membranes were treated with phospholipase D (PLD) to increase concentrations of PA within the membranes. Membranes were also treated with other phospholipases including phospholipase A2 (PLA2), and phospholipase C (PLC), which degrade phospholipids without generating PA. A phosphatidylinositol (PI) 3'-kinase inhibitor, LY294002, strongly and selectively inhibited intracellular calcium mobilization induced by PLD-treated membranes. This study suggests that PA-enriched plasma membranes, which exert their effects by activating a unique signaling pathway mediated by PI 3'-kinase, are potent, physiologically relevant initiators of neutrophil activation.
Bentz
M
M
Cellular Biochemistry Laboratory, Methodist Research Institute, Indianapolis, Indiana 46202, USA.
Harvey
K
K
Burtschi
D J
DJ
English
D
D
Siddiqui
R A
RA
D016227:Benzoquinones; D020013:Calcium Signaling / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D047029:Lactams, Macrocyclic; D009025:Morpholines / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010739:Phospholipase D / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017828:Rifabutin / Q000031:analogs & derivatives; D010738:Type C Phospholipases / Q000494:pharmacology
D016227:Benzoquinones; D002867:Chromones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D009025:Morpholines; D010712:Phosphatidic Acids; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010980:Platelet Membrane Glycoproteins; D011809:Quinones; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D017828:Rifabutin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D010739:Phospholipase D