Localization of cationic proteins derived from platelets and polymorphonuclear neutrophils and local loss of anionic sites in glomeruli of rabbits with experimentally-induced acute serum sickness.

The localization of cationic proteins (CP) derived from platelets and from polymorphonuclear neutrophils (PMN) in glomeruli of 42 rabbits injected i.v. with a large amount of bovine serum albumin, was investigated in sequential biopsies by immunofluorescence, using goat-anti-platelet CP and anti-PMN CP sera. Platelet CP deposits became detectable within 7 to 8 days after the i.v. injection of bovine serum albumin, before or coincident with the onset of proteinuria. The intensity and the extent of linear and segmental deposits of platelet CP along the glomerular capillary walls reached a peak at day 9 to 10, when proteinuria was maximal. The anti PMN-CP serum stained the cytoplasm of the few PMN present in glomeruli and only occasionally at day 11 and 12 identified focal deposits of PMN-CP along the glomerular capillary walls. The kinetic study of glomerular immune deposits showed that the first appearance of immune deposits in antigen excess was preceded by, or was concomitant, with the detection of platelet-CP in glomeruli. In the later stages of serum sickness, the immune deposits showed a progressive increase in rabbit IgG and C3. The glomerular polyanions were studied by light microscopy, using the colloidal iron technique, and by electron microscopy using polyethyleneimine as a cationic probe. The glomerular deposits of platelet-CP were associated with a reduction of colloidal iron staining, which was maximal 9 to 11 days after the i.v. injection of bovine serum albumin. At day 15, colloidal iron staining was almost completely restored. At day 9 in rabbits with acute serum sickness the anionic sites of glomerular basement membrane evidenced by polyethyleneimine, were segmentally decreased, mainly in the lamina rara interna. In rabbit studied at day 15 the anionic sites were decreased only at the base of the subepithelial electron dense deposits (humps). These results suggest that in rabbits with experimentally-induced acute serum sickness, during the early stages of glomerular immune deposit formation endogenous CP, released mainly from platelets, bind to glomerular capillary walls and possibly contribute to the neutralization of glomerular polyanions.