Macrophage-mediated suppression. I. Evidence for participation of both hydrogen 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 parvum-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.