Selective Suppression by Adherent Cells, Prostaglandin, and Cyclic AMP Analogues of Blastogenesis Induced by Different Mitogens

Depletion of adherent cells markedly enhances blastogenesis induced by the galactosyl-directed lectins, soybean agglutinin, peanut agglutinin, and hepatic binding protein, but has little effect on lymphocyte blastogenesis induced by phytohemagglutinin or concanavalin A. Treatment of unfractionated lymphocytes with indomethacin and other agents that inhibit prostaglandin synthesis mimics the selective effect of removing adherent cells. After depletion of adherent cells, these agents no longer affect mitogen-induced blastogenesis. Treatment of lymphocytes that had been depleted of adherent cells with prostaglandin E1 selectively suppresses responses to hepatic binding protein, peanut agglutinin, and soybean agglutinin, whereas responses to phytohemagglutinin and concanavalin A are less affected. Cyclic AMP analogues and an inhibitor of cyclic AMP phosphodiesterase, methyl isobutyl xanthine, also selectively suppress responses to the galactosyl-directed lectins. Prostaglandin E1, cyclic AMP analogues, and methyl isobutyl xanthine are most effective when added early in the course of lymphocyte activation. Prostaglandin E1 levels are similar in the culture media of cells treated with the different mitogens, and are suppressed by both indomethacin and the removal of adherent cells. The data indicate that cells stimulated by different mitogens differ markedly in their sensitivity to suppression by similar levels of prostaglandin. The gradation of sensitivity to prostaglandin and to cyclic AMP of blastogenesis induced by the various mitogens studied, from most to least sensitive, is: hepatic binding protein ≧ peanut agglutinin > soybean agglutinin > concanavalin A > phytohemagglutinin.