Treatment with proteolytic enzymes decreases glomerular immune complex deposits in passive serum sickness in rats and mice

This study assessed the effect of protease treatment on glomerular immune complex (IC) deposition in passive serum sickness. IC containing 2.2 mg of specific rabbit antibovine gammaglobulin (Ab) and cationic bovine gammaglobulin (CBGG) at 5-fold antigen excess were given via tail vein to 140 g Sprague-Dawley rats; some rats received IC containing 125I-Ab. After maximal glomerular IC deposition (1h) a single intravenous dose of either 4 mg chymopapain plus 2 mg subtilisin (T), or saline (C) was given. By immunofluorescence (IF) 1 h later, 1/13 T rats had bright capillary wall deposits of CBGG vs 10/11 C rats (x2 = 13.4, p < .001); 6/13 T rats had Ab vs. 10/11 C rats (x2 = 4.05, p < .05). Isolated glomeruli from T rats given 125I-IC had 25% less Ab (3267 +/- 293 cpm/mg glomerular protein) than C rats (4327 +/- 530, p < .005). 20 g BALB/c mice given IC with CBGG and 0.3 mg Ab, or IC with native BGG (nBGG) and 1 mg Ab via tail vein received 0.5 mg chymopapain and 0.25 mg subtilisin in 5 divided intraperitoneal doses q 10 min beginning 1 h later. 20 min after the last dose, 2/15 T mice given CBGG-IC had capillary wall Ab deposits by IF vs 13/16 C mice (x2 = 11.7, p < .001). 1/16 T mice given nBGG-IC had mesangial Ab deposits vs. 11/15 C mice (x2 = 10.8, p < .001). The authors conclude that protease treatment can remove glomerular IC deposits