Hydrogen-peroxide-induced arachidonic acid metabolism in the rat alveolar macrophage.
Mounting evidence suggests that reactive oxygen metabolites can initiate the release and metabolism of arachidonic acid (AA). We therefore examined the effects of hydrogen peroxide (H2O2), a biologically relevant oxygen metabolite, on AA release and cyclooxygenase metabolism by the rat alveolar macrophage (AM). At concentrations between 10(-4) and 10(-3) M, which were largely noncytotoxic as assessed by chromium release, H2O2 exposure for 30 min caused a steep dose-dependent increase in AA release that peaked at approximately 5-fold stimulation at 10(-3) M H2O2. AA release induced by H2O2 was inhibited by the H2O2 scavenger catalase, but not by inactivated catalase or by scavengers of superoxide anion, hydroxyl radical, or ferric iron. An evaluation of cyclooxygenase metabolite formation by specific radioimmunoassays and high performance liquid chromatography demonstrated a greater than 2-fold increment in thromboxane (Tx)A2 (measured as TxB2) synthesis at 10(-4) M H2O2, but no increment in prostaglandin (PG) E2 synthesis. H2O2-induced TxB2 synthesis was cyclooxygenase-dependent, since it was inhibited by indomethacin (1 microM). There was no significant degradation of either PGE2 or TxB2 in AM cultures by H2O2 at concentrations to 10(-2) M. The effect of H2O2 on agonist-induced cyclooxygenase metabolism was also examined. H2O2 at 10(-4) M inhibited PGE2 synthesis induced by zymosan and A23187, whereas agonist-induced TxB2 synthesis was either unaffected (zymosan) or augmented (A23187) by H2O2. These findings suggest inhibition by H2O2 of PGE2 synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D015232:Dinoprostone; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology* / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D011919:Rats, Inbred Strains; D013928:Thromboxane A2 / Q000096:biosynthesis; D015054:Zymosan / Q000494:pharmacology
D000975:Antioxidants; D001095:Arachidonic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D000001:Calcimycin; D013928:Thromboxane A2; D015054:Zymosan; D006861:Hydrogen Peroxide; D002374:Catalase; D015232:Dinoprostone