Inhibition of human lymphocyte proliferation and interleukin 2 production by platelet activating factor (PAF-acether): reversal by a specific antagonist, BN 52021.
When added to a 72 h culture of human peripheral blood mononuclear leukocytes stimulated with phytohemagglutinin, PAF-acether caused a significant inhibition (40-65%) of proliferation at concentrations of 10(-8) to 10(-6) M. This inhibition was reversed by the specific PAF antagonist, BN 52021. It was also reversed by indomethacin, suggesting that PAF-acether mediated this suppression via cyclooxygenase metabolites of arachidonic acid. IL-2 production, measured at 24 h of lymphocyte proliferation, was similarly impaired (50-66%) by 10(-8)-10(-6) M PAF-acether. IL-2 production was brought up to 90% of control values when both PAF-acether and BN 52021 (10(-4) M) were added together to the lymphocyte cultures. These studies suggest a significant immunoregulatory role for PAF-acether and a potential use of BN 52021 as a biological response modifier.
D000328:Adult; D002478:Cells, Cultured; D015232:Dinoprostone; D004224:Diterpenes; D046934:Ginkgolides; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis*; D007783:Lactones; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis
D004224:Diterpenes; D046934:Ginkgolides; D007376:Interleukin-2; D007783:Lactones; D010835:Phytohemagglutinins; D010936:Plant Extracts; D010972:Platelet Activating Factor; D011458:Prostaglandins E; D013929:Thromboxane B2; C045856:ginkgolide B; D015232:Dinoprostone; D007213:Indomethacin