Does Protease Inhibitor Inhibit Complement Activation Caused by the Immune Complex Associated with Islet Cell Surface Antibody?

Abstract

Sera containing islet cell surface antibody were obtained from seven children with insulin-dependent diabetes mellitus soon after the onset of disease. After incubation of 51Cr-labelled rat islet cells with islet cell surface antibody, human AB-type serum with or without nafamostat mesylate was added before further incubation. Radioactivity in the supernatant was measured to determine complement-dependent antibody-mediated cytotoxicity. Cytotoxicity in untreated sera [mean (+/- SD) 19.4 +/- 4.0%] was significantly (P less than 0.001) inhibited by ethyleneglycoltetraacetic acid (EGTA) (7.1 +/- 4.9%), ethylenediaminetetraacetic acid (EDTA) (2.5 +/- 0.9%) and nafamostat mesylate (2.8 +/- 1.8%). Cytotoxicity of nafamostat mesylate-treated serum was significantly (P less than 0.05) lower than that of EGTA-treated serum but not significantly different from that of EDTA-treated serum. There was no difference in cytotoxicity between nafamostat mesylate-treated and untreated, inactivated human serum. The results indicate that the protease inhibitor nafamostat mesylate completely inhibited the complement activation of the immune complex associated with islet cell surface antibody by the classical and alternative pathways.