The role of a phosphatidylcholine-specific phospholipase C in the production of diacylglycerol for nitric oxide synthesis in macrophages activated by IFN-gamma and LPS.
Murine macrophages activated by interferon (IFN)-gamma and bacterial lipopolysaccharide (LPS) produce large amounts of nitric oxide (NO), which is a critical mediator for a variety of biological functions. The expression of this inducible NO synthase (iNOS) involves a protein kinase C (PKC)-dependent pathway, but the mechanism for the PKC activation in this system is unclear. Through analysis of diacylglycerol (DAG) synthesis and choline metabolism in activated macrophages, direct evidence is provided that NO synthesis involves the activation of an unusual phosphatidylcholine-specific phospholipase C (PC-PLC) and not a phosphatidylinositol-specific phospholipase C (PI-PLC) or phospholipase D (PLD).
Sands
W A
WA
Department of Immunology, University of Glasgow, UK.
Clark
J S
JS
Liew
F Y
FY
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D002460:Cell Line; D002794:Choline / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism*; D004790:Enzyme Induction; D007295:Inositol Phosphates / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D009573:Nitrites / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins; D012477:Salmonella enteritidis; D010738:Type C Phospholipases / Q000378:metabolism*
D004075:Diglycerides; D007295:Inositol Phosphates; D008070:Lipopolysaccharides; D009573:Nitrites; D010169:Palmitic Acids; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D019308:Palmitic Acid; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010738:Type C Phospholipases; D010739:Phospholipase D; D002794:Choline