Effects of concanavalin A and a succinylated derivative on lymphocyte proliferation and cyclic nucleotide levels.

Abstract

To better define cell surface-related changes involved in lymphocyte activation, native concanavalin A (Con A) and succinylated Con A (Suc-Con A) were studied for their effects on proliferation and cyclic nucleotide levels of human peripheral blood lymphocytes. At optimal mitogenic concentrations, the 2 forms of Con A induce equivalent proliferation; the mitogenic activity of Con A progressively decreases above 50 .mu.g/ml. The mitogenic activity of Suc-Con A is not decreased even at 250 .mu.g/ml. Lymphocytes stimulated by a range of concentrations of Suc-Con A (25-250 .mu.g/ml) show progressive increases in levels of cyclic[c]GMP during the first 10 min of incubation. During the same period, native Con A induces initial increases in cGMP; above 25 .mu.g/ml, lymphocytes treated with Con A show concentration-dependent declines in the elevated cGMP levels. Although Suc-Con A has no significant effect on levels of cAMP, Con A produces increases that are concentration- and time-dependent. The concentrations of Con A responsible for the early declines in cGMP and the increases in cAMP levels are those which in parallel studies induce less lymphocyte proliferation. The consistent increase in cGMP levels caused by Con A and Suc-Con A suggests that cGMP is involved in the induction of the proliferative response. The increase in cAMP levels caused by Con A, but not by its succinylated derivative, may be responsible for the decrease in mitogenic potential observed with high doses of the native mitogen.