Inhibition of production of LTB 4 and chemotactic agent from rat alveolar macrophages treated with t-butyl hydroperoxide is independent of ATP depletion

Abstract

In rat alveolar macrophages treated with 100 μM t-butyl hydroperoxide (tBOOH), leukotriene B 4 (LTB 4) synthesis was significantly lower than the basal level while levels of cyclooxygenase pathway products were increased. LTB 4, 5,6-dihydroxyeicosatetraenoic acid (5,6-DiHETEs), and 5-hydroxyeicosatetraenoic acid (5-HETE) production in macrophages was significantly stimulated by 2 μM A23187, but this was suppressed 40% by simultaneous addition of 10 μM tBOOH and completely abolished by 100 μM tBOOH. Basal and A23187-stimulated macrophage production of chemotactic agents were similarly suppressed by addition of tBOOH; this effect paralleled depression of cellular LTB 4 synthesis. In contrast to the significant depression of A23187-stimulated formation of 5-lipoxygenase products by 10 μM tBOOH, cellular adenosine triphosphate (ATP) was unchanged. Macrophages pretreated with KCN led to a 42% decline in ATP levels; however, LTB 4, 5,6-DiHETEs, and 5-HETE production in response to A23187 was not suppressed. The results indicate that inhibition of 5-lipoxygenase pathway products in macrophages treated with tBOOH did not occur by depletion of cellular ATP levels.