PARTICIPATION OF PTERINS IN THE CONTROL OF LYMPHOCYTE STIMULATION AND LYMPHOBLAST PROLIFERATION

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (11) , 5356-5359
Abstract
Biopterin accumulation had been demonstrated as the result of normal and, especially, of malignant hemopoietic cell proliferation. Among 13 major intermediates of pterin metabolism and 2 lumazines, xanthopterin (but not dihydroxanthopterin) was found to inhibit cell proliferation (half-maximum inhibition at 1.8 .times. 10-5 M) during concanavalin A-induced lymphocyte activation in prestimulated lymphocytes, and in a lymphoid cell line grown in continuous culture (LS-2). LS-2 cells exposed to maximum inhibitor concentrations largely maintained the initial thymidine incorporation rate for .apprx. 40 h but failed to enter logarithmic growth. Isoxanthopterin inhibition was found only in serum-free medium, since it is trapped by the .alpha.-acid glycoprotein present in the serum. The reduced biopterin derivatives, sepiapterin, dihydrobiopterin and tetrahydrobiopterin, are costimulators during concanavalin A-induced lymphocyte activation. Their costimulatory effect follows an optimum curve and peaks at 1.5 to 3 .times. 10-5 M. It highest at the suboptimal and supraoptimal concanavalin A concentration. The D-erythro isomer dihydroneopterin was inactive. The results indicate that the anabolic-reduced biopterin derivatives are not simply lymphocytic products, but, in combination with the catabolites xanthopterin and isoxanthopterin, they also participate in the regulation of lymphocyte activation. Hence, they fulfill the criteria for lymphokines.