Abstract
We have previously demonstrated the involvement of platelet-activating factor (PAF), which was newly generated by resident mononuclear cells with PMA-stimulation, in the rat pleurisy induced by phorbol myristate acetate (PMA) .In the present study, we examined the mechanism of PAF production by mononuclear cells stimulated with PMA. Mononuclear cells from normal SD rats were incubated with PMA (1μM) at 37°C in the presence or absence of inhibitors. After a certain time of incubation, medium and cell fraction were extracted separately as previously reported. Mononuclear cells mainly produced C16-PAF, and the content in cell fraction peaked at 30 min as about 10 ng/107 cells. While PAF released in the medium was about 4 ng/107 cells at 30 to 60 min. Acetyltransferase activity in the cells stimulated by PMA increased at 10 min. Addition of p-BPB into the medium completely suppressed PMA-stimulated PAF production by mononuclear cells. While indomethacin and AA-861 did not affect the production. W-7, calmodulin inhibitor, and diltiazem, Ca2+ channel blocker, did not show significant reduction of PAF production. In contrast, staurosporine, c-kinase inhibitor, significantly reduced not only PAF production but also increased acetyltransferase activity.Therefore it seems likely that PMA-induced PAF production links with c-kinase system.
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