Differential dependence on protein kinase C of arachidonic acid metabolism stimulated by hydrogen peroxide and by zymosan in the alveolar macrophage

The dependence on protein kinase C (PKC) of arachidonic acid (AA) metabolism stimulated by the biologically important oxidant H₂O₂ as compared to zymosan particles, was investigated in the rat alveolar macrophage. The PKC inhibitor staurosporine markedly reduced AA release and eicosanoid synthesis stimulated by zymosan, but only slightly inhibited AA release and metabolism induced by H₂O₂. Furthermore, in macrophages depleted of PKC by extended exposure to phorbol 12-myristate 13-acetate, AA release in response to zymosan was greatly inhibited, whereas that stimulated by H₂O₂ was attenuated to a significantly lesser degree. Thus, zymosan-stimulated AA metabolism requires active PKC, whereas H₂O₂-induced metabolism is largely PKC-independent. This provides direct evidence for the existence of two pathways of agonist-stimulated AA metabolism, which differ in their dependence on PKC, in the alveolar macrophage.