Superoxide generation is inhibited by phospholipase A2 inhibitors. Role for phospholipase A2 in the activation of the NADPH oxidase.
The stimulation of O2.- generation by phorbol 12-myristate 13-acetate (PMA) in human neutrophil-derived cytoplasts was inhibited by a variety of phospholipase A2 inhibitors in a concentration-dependent manner. Inhibition was found to be independent of the order of addition of the inhibitor and PMA. The most potent inhibitor, RO 31-4639, inhibited O2.- generation with an IC50 value (concentration causing 50% inhibition) of 1.5 microM. The addition of either arachidonic acid or SDS, in the presence of the inhibitors, was able to restore O2.- generation. The results suggest that arachidonic acid, released by phospholipase A2, is necessary for both the activation and the maintenance of O2.- generation by the NADPH oxidase.
Henderson
L M
LM
Department of Biochemistry, School of Medical Sciences, University of Bristol, U.K.
Chappell
J B
JB
Jones
O T
OT
D000098:Acetophenones / Q000494:pharmacology; D000605:Amino Alcohols / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002474:Cell-Free System; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000378:metabolism*; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000098:Acetophenones; D000605:Amino Alcohols; D001095:Arachidonic Acids; D013481:Superoxides; C062204:Ro 31-4639; D016718:Arachidonic Acid; D012967:Sodium Dodecyl Sulfate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; D013755:Tetradecanoylphorbol Acetate; C006821:4-bromophenacyl bromide