Effects of Concanavalin A and a Succinylated Derivative on Lymphocyte Proliferation and Cyclic Nucleotide Levels

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 73; no. 5; pp. 1717 - 1721
• Main Authors: Hadden, John W., Hadden, Elba M., Sadlik, John R., Coffey, Ronald G.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01-05-1976; National Acad Sciences
• Subjects: Aggregation; Blood; Cell Division; Cell growth; Cell Membrane - ultrastructure; Concanavalin A - analogs & derivatives; Concanavalin A - pharmacology; Cyclic AMP - metabolism; Cyclic GMP - metabolism; Cyclic nucleotides; Dose-Response Relationship, Drug; Humans; Immunology; Kinetics; Lectins; Lymphocyte Activation - drug effects; Lymphocyte proliferation; Lymphocytes; Lymphocytes - metabolism; Lymphocytes - physiology; Lymphocytes - ultrastructure; Mitogens; Receptors; Structure-Activity Relationship
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.73.5.1717

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 μ g/ml. In contrast, the mitogenic activity of Suc-Con A is not decreased even at 250 μ g/ml. Lymphocytes stimulated by a range of concentrations of Suc-Con A (25-250 μ g/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 μ g/ml, lymphocytes treated with Con A show concentration-dependent 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 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.