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.
Fitzgerald
M F
MF
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent, U.K.
Parente
L
L
Whittle
B J
BJ
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D044482:Benzeneacetamides; D016861:Cyclooxygenase Inhibitors; D006168:Guinea Pigs; D006877:Hydroxamic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011863:Radioimmunoassay; D013929:Thromboxane B2 / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044482:Benzeneacetamides; D016861:Cyclooxygenase Inhibitors; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011720:Pyrazoles; C056616:N-(4-benzyloxybenzyl)acetohydroxamic acid; D007975:Leukotriene B4; D013929:Thromboxane B2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D001091:Arachidonate Lipoxygenases; D007213:Indomethacin