Glucocorticoids fail to inhibit arachidonic acid metabolism stimulated by hydrogen peroxide in the alveolar macrophage.
We have previously demonstrated that the biologically important oxidant hydrogen peroxide (H2O2) triggers release and metabolism of arachidonic acid (AA) in the alveolar macrophage (AM). In this study, we evaluated the ability of glucocorticoids to inhibit rat AM AA metabolism stimulated by H2O2, as compared to the particulate zymosan. Methylprednisolone and other glucocorticoids failed to significantly inhibit release of AA stimulated by H2O2, while markedly reducing AA release in response to zymosan. Similarly, methylprednisolone only weakly inhibited synthesis of thromboxane (Tx)B2 stimulated by H2O2, while inhibiting zymosan-induced eicosanoid synthesis to a marked degree. On the other hand, the phospholipase inhibitor mepacrine strongly inhibited AA release and TxB2 formation stimulated by both H2O2 and zymosan, indicating that H2O2 induced AA metabolism is indeed susceptible to pharmacologic inhibition. The failure of glucocorticoids to inhibit AA metabolism stimulated by H2O2 in the AM may in part explain their inability to ameliorate oxidant-mediated lung inflammation and injury.
Sporn
P H
PH
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0360.
Murphy
T M
TM
Peters-Golden
M
M
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D015777:Eicosanoids / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008775:Methylprednisolone / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015054:Zymosan / Q000494:pharmacology
D001095:Arachidonic Acids; D015777:Eicosanoids; D005938:Glucocorticoids; D015054:Zymosan; D006861:Hydrogen Peroxide; D011796:Quinacrine; D008775:Methylprednisolone