Macrophage-mediated suppression. I. Evidence for participation of both hdyrogen peroxide and prostaglandins in suppression of murine lymphocyte proliferation.
Macrophage-mediated suppression of Con A induced proliferation of murine splenic lymphocytes was studied in vitro. Either Corynebacterium parvrum-induced peritoneal exudate cells (PEC) or thioglycollate-induced PEC could totally suppress lymphocyte proliferation at a PEC:lymphocyte ratio of 2:10, whereas a ratio of 1 to 1.5: 10 caused a partial (60 to 68%) suppression. Exogenous PGE1 and PGE2 at concentrations of 10(-8) to 10(-6) M could not totally suppress lymphocyte proliferation. Conversely, indomethacin reversed the partial suppression by macrophages but only partially protected the totally suppressed lymphocyte cultures. Macrophage-mediated cytotoxicity and cytostasis have been proposed to be mediated by hydrogen peroxide. Therefore, hydrogen peroxide was investigated as a possible additional cause for macrophage-mediated suppression, by testing the anti-inhibitory effects of catalase. Partially suppressed cultures were effectively protected from suppression by catalase. In totally suppressed cultures, catalase alone was only minimally effective, but a synergistic effect of catalase and indomethacin was obtained, which provided complete protection from maximal macrophage-mediated suppression. Catalase presumably contributes to the reversal of macrophage suppressive effects both by reducing the direct toxic effect of H2O2 and by preventing the H2O2 from generating additional prostaglandins.
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D002374:Catalase / Q000494:pharmacology; D002455:Cell Division; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D007213:Indomethacin / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011425:Propionibacterium acnes / Q000276:immunology; D011453:Prostaglandins / Q000494:pharmacology*
D011453:Prostaglandins; D006861:Hydrogen Peroxide; D002374:Catalase; D007213:Indomethacin