Ultrastructural Localization of the Three Major Basement Membrane Components-Type IV Collagen, Heparan Sulf ate Proteoglycan and Laminin – in Human Membranous Glomerulonephritis

Abstract

Membranous glomerulonephritis (MN) is characterized by the presence of subepithelial immune complexes and thickening of the glomerular basement membrane (GBM). Immune complexes are recognized as subepithelial electron-dense deposits (EDDs) by electron microscopy. We used immunogold electron microscopy to detect the GBM components--type IV collagen, heparan sulfate proteoglycan (HS-PG) and laminin--in thickened GBM, and studied the relationship between immune complexes and these GBM components. We demonstrate that the three major basement membrane components are distributed throughout the newly synthesized GBM. These findings suggest that type IV collagen, HS-PG, and laminin together comprise the spike-like structures and the newly synthesized GBM-like matrix in the thickened GBM of idiopathic MN and membranous lupus nephritis. The newly constructed matrix in the GBM appears to be composed of nearly normal GBM. In type IV collagen, the alpha 1-chain was rarely present on the newly synthesized basement membrane in the lamina rara externa, while alpha 3-chain was present on the subepithelial newly synthesized basement membrane. HS-PG was found within EDDs in membranous lupus nephritis. This suggests that anti-DNA antibody may cross-react with the HS-PG component of the GBM and thus form a subepithelial immune complex.