Differential dependence on protein kinase C of arachidonic acid metabolism stimulated by hydrogen peroxide and by zymosan in the alveolar macrophage.
The dependence on protein kinase C (PKC) of arachidonic acid (AA) metabolism stimulated by the biologically important oxidant H2O2, as compared to zymosan particles, was investigated in the rat alveolar macrophage. The PKC inhibitor staurosporine markedly reduced AA release and eicosanoid synthesis stimulated by zymosan, but only slightly inhibited AA release and metabolism induced by H2O2. Furthermore, in macrophages depleted of PKC by extended exposure to phorbol 12-myristate 13-acetate, AA release in response to zymosan was greatly inhibited, whereas that stimulated by H2O2 was attenuated to a significantly lesser degree. Thus, zymosan-stimulated AA metabolism requires active PKC, whereas H2O2-induced metabolism is largely PKC-independent. This provides direct evidence for the existence of two pathways of agonist-stimulated AA metabolism, which differ in their dependence on PKC, in the alveolar macrophage.
Sporn
P H
PH
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360.
Marshall
T M
TM
Peters-Golden
M
M
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D015777:Eicosanoids / Q000096:biosynthesis; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology*
D000470:Alkaloids; D001095:Arachidonic Acids; D015777:Eicosanoids; D010703:Phorbol Esters; C008876:phorbol-12,13-didecanoate; D016718:Arachidonic Acid; D015054:Zymosan; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate