Effect of E-64, thiol protease inhibitor, on the secondary anti-SRBC response in vitro.
E-64, L-trans-epoxysuccinyl- leucylamido (4-guanidino) butane, a specific inhibitor of thiol proteases originally isolated from the culture of a fungus, was examined in connection with the immune responses to the splenocytes of mice. In cultures of C3H/He mouse splenocytes, E-64 and its analogues showed mitogenic activity, and some of them enhanced the lymphocyte blast transformation induced by a suboptimal concentration of concanavalin A. E-64 caused a significant suppressive effect on the secondary anti-SRBC responses when 7- or 14-day-primed BDF1 mouse splenocytes were cultured with SRBC, while it induced no effect on cultured splenocytes either from mice treated with cyclophosphamide, from mice sensitized with dinitrophenyl-Ficoll. The results with E-64 and its close analogues revealed that their effects on the immune response roughly correlated with their inhibitory activity against thiol protease. These results suggest that a thiol protease might be involved in the process of secondary immune response in mouse splenocytes.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives / Q000494:pharmacology; D007156:Immunologic Memory / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008934:Mitogens / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D012756:Sheep / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology
C031007:DNP-Ficoll; D008934:Mitogens; D011480:Protease Inhibitors; D003208:Concanavalin A; D014107:Tosyllysine Chloromethyl Ketone; D005362:Ficoll; D003520:Cyclophosphamide; D007930:Leucine; C024974:E 64