Hydrogen-peroxide-induced arachidonic acid metabolism in the rat alveolar macrophage

P. H S Sporn, M. Peters-Golden, R. H. Simon

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35 Scopus citations


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 51chromium release, H2O2 exposure for 30 min caused a steep dose-dependent increase in AA release that peaked at ~ 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 >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 μM). 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 inhibited PGE2 synthesis induced by zymosan and A23187, wherease agonist-induced TxB2 synthesis was either unaffected (zymosan) or augmented (A23187) by H2O2. These findings suggest inhibition by H2O2 of PGE2 synthesis. The capacity of H2O2 to induce AA release and to specifically alter the relative amounts of PGE2 and TxB2 produced by the AM suggest a mechanism by which oxidant-mediated lung inflammation and injury may be amplified or modulated by AM-derived metabolites of AA.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalAmerican Review of Respiratory Disease
Issue number1
StatePublished - Jan 1 1988

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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