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.