Effects of L-asparaginase on lymphocyte surface and blastogenesis.

Summary l-Asparaginase is immunosuppressive, inhibiting both the cellular and humoral responses, as well as the concanavalin A-and/or phytohemagglutinin-induced blastogenesis of lymphocytes. However, its mechanism of action is presently unclear. This study dealt with the enzyme effects on the lymphocyte surface leading to interference with the binding of concanavalin A. The mitogen was labeled with 125 I and added to lymphocyte cultures prior to or following incubation with l-asparaginase. The data permitted the following conclusions. l-Asparaginase treatment prior to introduction of mitogen reduced the capacity of the lymphocyte to bind concanavalin A. Enzymatic treatment of lymphocytes 90 min after the introduction of mitogen did not influence this binding. Addition of l-asparagine, l-glutamine, and aspartic acid did not reverse the inhibitory effects of the enzyme. The decrease in mitogen binding (20%) led to a 95% decrease in subsequent DNA synthesis. Mitogen binding to receptors on lymphocytes precedes their subsequent stimulation. It appears that the decrease of mitogen binding by l-asparaginase results from an alteration on the lymphocyte surface. Any such alteration by the enzyme could account for its immunosuppressive activity.