Glomerular injury induced by antibodies against heparan sulfate proteoglycan (HSPG) derived from PYS 2 cells

Kidneys of Balb/c mice intravenously injected with rabbit antibodies to heparan sulfate proteoglycan (HSPG) derived from PYS-2 cells were studied for 14 weeks. Antibodies were found to bind to the glomerular basement membrane (GBM) as early as 15 min after the injection. Binding of antibodies was observed over the whole thickness of the GBM. The lamina rara interna and foot process base appeared to be more intensely stained. This pattern did not change throughout the experiments. Mild inflammatory changes (infiltration of polymorphonuclear cells and swelling of the glomerular endothelium) were seen at the initial stage (~1 day), and mesangial expansion followed (1–4 weeks). In mice pre- and booster-immunized with normal rabbit IgG, a moderate autologous response was observed by immunofluorescence microscopy, but no significant inflammatory changes were noted. At the late stage (6 weeks ~), irregular GBM thickening was observed. The thickening was due mainly to expansion of the lamina rara externa. These findings suggest that the anti-HSPG antibodies caused mild glomerulonephritis at the initial stage, and later caused thickening of the GBM possibly by disturbing the assembly, production and degradation of GBM components.