Inhibition by XXXX of zymosan-induced leukotriene synthesis in alveolar macrophages.

@entity1667 @entity251 @entity1420 @entity55 @entity12032 @entity1426 @entity7489 @entity3448 @entity3899 @entity35 @entity1813 @entity10769
Alveolar-macrophage-derived @entity12032 metabolites of @entity1426 (AA) are thought to be important mediators of @entity55 and injury. Inhibition of AA metabolism may be an important anti-inflammatory mechanism of glucocorticoid (GC) action. In the present study, we have examined the effect of @entity1667 (MP) on leukotriene (LT) B4 and LTC4 synthesis by cultured @entity35 alveolar macrophages (AMs) stimulated with the proinflammatory particle zymosan. Zymosan stimulation resulted in the formation of LTB4 greater than @entity7489 ( @entity3448 ) greater than LTC4 as assessed by both high performance liquid chromatography and radioimmunoassay. Sixteen hours of pretreatment with 1 microM MP maximally inhibited synthesis of @entity3448 by 76 +/- 4%, LTB4 by 83 +/- 3%, and LTC4 by 91 +/- 3%. The inhibition of @entity1813 was specific, as the sex hormones @entity1420 , @entity251 , and @entity10769 had no consistent effect. Inhibition was dose-dependent, with 50% inhibition of synthesis occurring at 10(-7) M for @entity3448 , but at 10(-8) M for both LTB4 and LTC4. Pretreatment with MP for only 1 h inhibited LTC4 production (42 +/- 3%) to a greater extent than either @entity3448 (25 +/- 1%) or LTB4 (14 +/- 7%). These data indicate that MP significantly and substantially inhibits zymosan-induced LTB4 and LTC4 synthesis. Furthermore, the greater degree, greater potency, and faster onset of action for MP inhibition of LT synthesis than of @entity3448 synthesis suggest the possibility that MP may exert postphospholipase effect(s) on LT synthesis. These results support the possibility that modulation of AM @entity3899 metabolism may represent an important anti-inflammatory mechanism of GC action in the lung.
