Release of PAF-acether and eicosanoids from guinea-pig alveolar macrophages by FMLP: effect of cyclo-oxygenase and lipoxygenase inhibition.

Adherent guinea-pig alveolar macrophages stimulated in vitro with FMLP (1 microM) for 5-60 min released PAF-acether, TXB2 and LTB4, with maximal levels being achieved after a 5 min incubation. The levels of eicosanoids were maintained during the 60 min incubation period, whereas the levels of PAF-acether decreased and were no longer detectable after 60 min incubation. Indomethacin (1 microM) completely suppressed the release of TXB2 stimulated by FMLP (1 microM for 5 min) whilst potentiating the release of LTB4. The selective 5-lipoxygenase inhibitor, BW A137C (1 microM), abolished the stimulated release of LTB4 without affecting the release of TXB2. BW755C (1-20 microM) caused a dose-related inhibition of TXB2 release but did not affect LTB4 release, while none of the drugs studied affected the release of PAF-acether. These results indicate that the FMLP-induced release of PAF-acether from guinea-pig alveolar macrophages is not susceptible to modulation by selective inhibition of lipoxygenase or cyclo-oxygenase and is therefore not secondary to the synthesis of LTB4 or TXB2.