Relationship of glucocorticoid suppression of arachidonic acid metabolism to alteration of neutrophil function.
The role of arachidonic acid metabolism in glucocorticoid-induced suppression of neutrophil function was investigated. In vivo treatment of cattle with dexamethasone decreased the production of lipoxygenase products of arachidonic acid metabolism (leukotriene B4 [LTB4] and H-5-hydroxy-6,8,11,14-eicosatetraenoic acid [5-HETE]) in neutrophils. We previously reported that in vivo dexamethasone treatment resulted in alteration of in vitro neutrophil oxidative metabolism, iodination, antibody-dependent cell-mediated cytotoxicity (ADCC), and random migration. To determine if the decrease in production of LTB4 and 5-HETE were responsible for the changes in neutrophil function, neutrophils were treated in vitro with inhibitors of the lipoxygenase enzyme (BW755c and nordihydroguaiaretic acid), and their function was evaluated. A decrease in neutrophil oxidative metabolism and iodination was observed, but there was no effect on neutrophil random migration or ADCC. The results suggest that in vivo treatment with glucocorticoids inhibit neutrophil oxidative metabolism and iodination by decreasing the formation of lipoxygenase products of arachidonic acid metabolism but alter neutrophil random migration and ADCC by a mechanism independent of arachidonic acid metabolism.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002417:Cattle; D003907:Dexamethasone / Q000494:pharmacology*; D004075:Diglycerides / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D009637:Masoprocol / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D015054:Zymosan / Q000494:pharmacology
D001095:Arachidonic Acids; D004075:Diglycerides; D006893:Hydroxyeicosatetraenoic Acids; D010743:Phospholipids; D011720:Pyrazoles; D014280:Triglycerides; D007975:Leukotriene B4; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D003907:Dexamethasone; D015054:Zymosan; D007213:Indomethacin