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, we studied native concanavalin A (Con A) and succinylated concanavalin A (Suc-Con A) for their effects on proliferation and cyclic nucleotide levels of human peripheral blood lymphocytes. At optimal mitogenic concentrations, the two forms of Con A induce equivalent proliferation; however, the mitogenic activity of Con A progressively decreases above 50 Mg/ml. In contrast, the mitogenic activity of Suc-Con A is not decreased even at 250 qg/ml.Lymphocytes stimulated by a range of concentrations of SueCon A (25-250 gg/ml) show progressive increases in levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP) during the first 10 min of incubation. During the same period, native Con A induces initial increases in cyclic GMP; however, above 25 jsg/ml, lymphocytes treated with Con A show concentrationdependent declines in the elevated cyclic GMP levels. Although Suc-Con A has no significant effect on levels of adenosine 3': 5'-cyclic monophosphate (cyclic AMP), Con A produces increases that are concentration-and time-dependent. The concentrations of Con A responsible for the early declines in cyclic GMP and the increases in cyclic AMP levels are those which in parallel studies induce less lymphocyte proliferation. The consistent increase in cyclic GMP levels caused by both Con A and Suc-Con A suggests that cyclic GMP is involved in the induction of the proliferative response. The increase in cyclic AMP levels caused byCon A, but not by its succinylated derivative, may be responsible for the decrease in mitogenic potential observed with high doses of the native mitogen.

Analysis of the stimulation-inhibition paradox exhibited by lymphocytes exposed to concanavalin A.

“…This event therefore reflects the blockade by high doses of Con A, rather than the committed state of the cells; the increases in amino acid transport must occur after the point of the blockade, and therefore after commitment. Similarly, the increases in cyclic GMP levels after lectin binding, which have been considered as possible inductive events in mitogenesis (21), follow the pattern of a postcommitment rather than a precommitment event.…”

Metabolic stimulation of polymorphonuclear leucocytes: Effects of tetravalent and divalent concanavalin A

“…In fact, fragments of antibodies or lectin derivatives with reduced valency, but with unaltered receptor binding properties, usually induce modified cell responses with respect to the parent molecule [5-7, 11, 18]. For example, divalent succinyl-Con A stimulates lymphocyte growth but, unlike the parent tetravalent lectin, shows no inhibition of mitogenesis [6,7,33]. Unlike Con A, succinyl-Con A also fails to inhibit virus release from infected cells [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18].…”

Inhibition of herpes simplex virus replication by succinyl concanavalin A

“…In addition, the binding of ConA to mouse peritoneal macrophages was shown to result in the induction of lysosomal enzymes (17). Although little is known about the mechanism of action involved in surface level regulation, it is likely that under certain circumstances these actions are mediated through so-called second messengers, including cyclic AMP, cyclic GMP, or calcium (10,22). These substances, in turn, may produce their effects through the alteration of phosphorylation patterns of specific cellular proteins (20).…”