Role of icosanoids in alveolar macrophage phagocytosis and aggregation.
Rat alveolar macrophages (AM) collected by bronchoalveolar lavage were incubated in the presence or absence of various icosanoids or inhibitors of the arachidonic acid cascade with either chrysotile asbestos (50 micrograms/ml) to determine cell aggregation, or human red blood cells (Rh+; preincubated with anti-D globulin) to measure phagocytosis. Phorbol myristate acetate (PMA) and ionophore A23187, two agents which stimulate arachidonic acid metabolism, reduced red blood cell phagocytosis by AM whereas arachidonic acid had no effect on this cellular event. Neither arachidonic acid nor its metabolites (prostaglandins E2, I2, F2 alpha, the thromboxane mimick U44069 and leukotrienes A4, B4, C4, D4) had a significant effect on phagocytosis. Inhibition of the synthesis of cyclooxygenase products with various concentrations of indomethacin, aspirin and OKY-1581 or of lipoxygenase products with eicosatetraynoic acid, BW755c, diethylcarbamazine and phenidone did not affect phagocytosis either. On the other hand, asbestos-induced aggregation was significantly reduced by nordihydroguaiaretic acid (NDGA), BW755C, benoxaprofen, and high concentrations of indomethacin but not by aspirin. These results suggested that metabolites of arachidonic acid (especially lipoxygenase products) play a modulatory role in non specific alveolar macrophage aggregation but not in specific, Fc receptor-mediated phagocytosis.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000502:physiology*; D001194:Asbestos / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D011422:Propionates / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D018029:Rho(D) Immune Globulin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D007136:Immunoglobulins; D016859:Lipoxygenase Inhibitors; D011422:Propionates; D018029:Rho(D) Immune Globulin; D001194:Asbestos; C011677:benoxaprofen; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin