t-Butyl hydroperoxide stimulates alveolar macrophage biosynthesis of cyclooxygenase products

Rat alveolar macrophages, labeled with ³H-arachidonic acid, were treated with t-butyl hydroperoxide (tBOOH). Treatment of cells with 100 μM tBOOH led to a rapid increase in 12-hydroxyheptadecatrienoic acid (12-HHT) within 2.5 minutes. At 15 minutes, 12-HHT levels appeared to plateau as there was not further increase at 30 minutes. TxB₂ levels increased in a similar manner to that found with 12-HHT; however, only the level at 15 minutes was statistically increased. TxB₂ levels also appeared to plateau at 15 minutes. Indomethacin, at a concentration of 1 μM, significantly inhibited TxB₂ and 12-HHT production by approximately 90%. Desferal, an iron chelator, had no effect on alterations of biosynthesis of cyclooxygenase products by macrophages treated with tBOOH. No evidence of lipoxygenase products was found. Thus, these results suggest that tBOOH rapidly and selectively stimulated arachidonic acid metabolism through the cyclooxygenase pathway in rat alveolar macrophages. The stimulation of cyclooxygenase activity was transient with a maximum rate observed at 100 μM tBOOH.