ULTRASTRUCTURAL CHANGE OF THE GLOMERULAR-BASEMENT-MEMBRANE IN RATS WITH HEYMANN NEPHRITIS REVEALED BY ULTRAHIGH-RESOLUTION SCANNING ELECTRON-MICROSCOPY

To assess the relationship between the glomerular injury induced by im mune complex deposition and proteinuria, ultrastructural changes of th e glomerular basement membrane (GBM) were investigated in Heymann neph ritis. Active Heymann nephritis was induced in rats by injecting them with tubular brush border antigen, known as Fx1A, emulsified in comple te Freund's adjuvant (CFA). Measurement of urinary protein excretion a nd histological examinations were carried out for up to 15 weeks after immunization. Proteinuria developed in rats within 10 weeks of immuni zation and coincided with the development of subepithelial deposits wi th minimal spike-like basement membrane protrusion. Acellular glomerul i were prepared by detergent treatment and were subjected to tannic ac id-osmium conductive staining prior to examination with an ultrahigh r esolution scanning electron microscope (HSEM). HSEM of the acellular G BM prepared from control rats injected with CFA alone revealed a meshw ork structure, with pores of about 9 nm in diameter. Proteinuric rats immunized with Fx1A showed a loosened meshwork structure, with pores o f about 15 nm in the acellular GBM adjacent to the deposits. The newly formed GBM overlying the deposit consisted of a meshwork structure as sociated with unorganized thin fibrils. Ultrastructural changes were n ever seen in GBM devoid of deposits. These findings indicate that sube pithelial deposits are closely involved in the development of proteinu ria by injuring the size selectivity of the GBM.