The polyvalent protease inhibitor, trasylol, inhibits DNA synthesis of mouse lymphocytes by an indirect mechanism.

By the use of incorporation of radiolabeled thymidine, uridine, and leucine into mouse lymphocytes, the inhibitory effect of the protease inhibitor, trasylol, on antigenor mitogen-induced lymphocyte triggering was studied in vitro. DNA synthesis, as well as RNA and protein syntheses, were effectively inhibited by 0.3–2.5 × 10^?7 mol of trasylol when responses were induced by homologous antigen, allogeneic cells, phytohemagglutinin, or endotoxic lipopolysaccharide of Escherichia coli. The inhibitory effect of trasylol was reversible. On the contrary, DNA synthesis by nonadherent spleen cells was hardly inhibited by the inhibitor when the cells were stimulated with a relatively large amount of concanavalin A. Antigen-induced DNA synthesis by non-adherent lymph node cells was enhanced by the culture supernatant of macrophages. This helping effect of macrophage supernatant was effectively inhibited either by soluble or insoluble trasylol. These results suggest that the inhibitory action of trasylol on lymphocyte triggering may operate indirectly to interfere with the helping action of macrophages on lymphocytes.