[Immunopharmacological actions of 6-amidino-2-naphthyl-4-guanidinobenzoate (FUT-175). 1. Effect of FUT-175 on immune response and host defense in mice].
FUT-175 is a new synthetic protease inhibitor which strongly inhibits complement-mediated hemolysis via the classical and alternative pathways. The present study was undertaken to examine the effects of FUT-175 on antibody formation and host defense in mice since the complement system participates in both immunological responses and host defense against bacterial infection. FUT-175 did not suppress the primary IgM and IgG antibody responses to sheep red blood cells, although FUT-175 was given at 10 to 100 mg/kg/day p.o. for 3 days before or after immunization. On the other hand, the primary anti-DNP IgE antibody response to DNP-conjugated ovalbumin was slightly suppressed only by post-administration of FUT-175 in a dose of 100 mg/kg/day p.o. for 5 days. However, the results of the adoptive transfer experiments indicate that FUT-175 did not affect either T cells or B cells participating in the secondary anti-DNP IgE antibody formation. FUT-175 in a dose of 10(-4)M but not at 10(-6) to 10(-5)M significantly decreased the proliferation of spleen cells caused by concanavalin A, lipopolysaccharide or the one-way mixed lymphocytes culture reaction using 1000 R-irradiated spleen cells from BDF1 mice as stimulator cells and those from C57BL/6 mice as responder cells. FUT-175 had an inhibitory rather than an enhancing effect on host defense to infection with Escherichia coli when administered at 10 to 100 mg/kg/day p.o. for 3 days before or after infection. These results strongly suggest that FUT-175 does not affect antibody formation and host defense in mice.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001424:Bacterial Infections / Q000276:immunology; D001550:Benzamidines; D006146:Guanidines / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects*; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011480:Protease Inhibitors / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects
D001550:Benzamidines; D006146:Guanidines; D011480:Protease Inhibitors; C032855:nafamostat