Removal of glomerular immune complexes in passive serum sickness nephritis by treatment in vivo with proteolytic enzymes.

The effect of in vivo protease treatment on glomerular immune complex deposits was investigated in passive serum sickness in mice and rats. BALB/c mice were injected intravenously with soluble immune complexes (IC) of cationic bovine gamma-globulin (BGG) antigen and rabbit anti-BGG antibody, or IC of native BGG and rabbit antibody. One hour after receiving IC, the time of maximal deposition, the mice were treated with chymopapain and subtilisin via five intraperitoneal doses at 10-minute intervals, and they were sacrificed 20 minutes after the last treatment. Only 2 of 15 treated mice given cationic IC had capillary wall deposits of antibody versus 13 of 16 control mice (p less than 0.001); only 1 of 16 treated mice given the more neutral IC had mesangial antibody deposits versus 11 of 16 control mice (p less than 0.001). Differences in BGG antigen were not apparent. In parallel studies, soluble IC containing rabbit antibody and cationic BGG antigen were administered intravenously to rats. After 1 hour, the rats received a single intravenous dose of chymopapain and subtilisin. Ninety minutes later the rats were sacrificed. As determined by immunofluorescence microscopy only 1 of 13 enzyme-treated rats had bright capillary wall deposits of BGG antigen versus 10 of 11 control rats (p less than 0.001); only 6 of 13 treated rats had deposits of rabbit antibody versus 10 of 11 control rats (p less than 0.05). Glomeruli isolated from enzyme-treated rats that had been injected with radioactive IC contained 44% less radioactivity (p less than 0.005). These observations indicate that treatment with proteases can promote the removal of glomerular IC deposits in vivo.