Proteinuria and structural alterations in rat glomerular basement membranes induced by intravenously injected anti-laminin immunoglobulin G.

Abstract

Antibodies against laminin, which is a defined glycoprotein of basement membranes, were produced in sheep and affinity purified by immunoadsorption on laminin-Sepharose (S.alpha.L). When injected i.v. into rats, S.alpha.L rapidly bound in a linear pattern to the glomerular basement membrane (GBM) in the peripheral and mesangial regions of all glomeruli, and, when > 0.5 mg S.alpha.L was injected, to some tubular BM. Horseradish peroxidase (HRP) reaction product was present throughout the full thickness of the GBM and mesangial matrix 1-2 h after the injection of conjugates of HRP and S.alpha.L. [125I]S.alpha.L binding to kidney in vivo increased linearly over the dose range of 40-950 .mu.g of IgG and accounted for .apprx. 2% of the injected dose/g kidney. When 4 mg of [125I]S.alpha.L was injected, 1.5% or 62 .mu.g/g kidney was bound. Proteinuria did not develop within 7 wk of injection in rats that received 0.5-1.6 mg of S.alpha.L. All animals that received injections of 4 mg of S.alpha.L gradually became proteinuric within 3-6 wk. Thickening, reduplication and flocculent subendothelial deposits were observed in the GBM of these animals. Mononuclear cells adhered to the GBM and infiltrated beneath the endothelium. The deposition of rat C3 [complement component 3] was infrequently observed, and rat IgG was not seen in the glomeruli of any rat that received S.alpha.L. Ten wk after injection, much greater amounts of S.alpha.L appeared within the mesangium than the peripheral GBM. The interaction of S.alpha.L with the GBM, possibly in concert with infiltrating mononuclear cells, gradually altered the structure and permeability characteristics of the glomerulus independent of a host anti-S.alpha.L humoral response.