The effect of protamine sulfate on the course of immune complex glomerulonephritis in the rat

In vivo studies in rats demonstrated that the binding of a highly cationic antigen (cationized human IgG, pI greater than 9.5) to glomerular polyanion could be significantly reduced by prior application of a small polycation, protamine sulfate. The degree of inhibition was dose dependent and the highest dose used, 4 mg/100 g body weight, reduced antigen binding by approximately 70%. In further experiments the ability of protamine sulfate to enhance elimination of cationic antigen-antibody immune complexes from the glomerular capillary wall was examined. Daily treatment with protamine sulfate, starting after induction of nephritis, produced a significant but only moderate reduction in the persistence of the antigen, without having any effect on proteinuria. Proteinuria could only be prevented when protamine sulfate was given immediately before induction of nephritis. Protamine sulfate had little influence on the course of established renal disease in the model employed. These results do not substantiate the concept of charge competition as a potentially useful therapeutic strategy.