DISTRIBUTION OF THE EXTRACELLULAR-MATRIX COMPONENTS IN HUMAN GLOMERULAR-LESIONS

Most glomerular pathologies are associated with alterations of the matrix compartment. Using reagents directed against the a1/a2 and a3 chains of type IV collagen [a1/a2(IV), a3(IV)], laminin, heparan sulphate proteoglycan (HPG), fibronectin, collagen I, and collagen III, we investigated the modifications of the glomerular matrix components in several human glomerular lesions compared with normal kidney. In type I membranous glomerulonephritis (MGN) (nine cases), we did not observe alterations in the matrix component distribution. In MGN types II and III (five cases), the spikes and chainettes were made of the a3(IV) chain, laminin, and HPG, while the a1/a2(IV) chains were localized along the subendothelial side of the glomerular basement membrane (GBM). In focal and segmental glomerulosclerosis (six cases), fibronectin, a1/a2(IV) chains, laminin, and small amounts of interstitial collagens were detected within the collapsed capillary loops; the newly formed matrix material between the podocytes and the GBM contained the a1/a2(IV) chains, laminin, and HPG but not the a3(IV) chain. In crescentic glomerulonephritis (six cases), fibronectin was the most abundant and, in purely cellular crescents, the unique component. A basement membrane-Iike network containing laminin, HPG, a1/a2(IV) chains, and interstitial collagens developed in a second step between the crescent cells. Interstitial collagens were present in the crescent framework, even when the integrity of Bowman's capsule was preserved. In membranoproliferative glomerulonephritis (five cases), we observed strong accumulation of fibronectin in the thickened mesangial spaces together with accumulation of laminin, a1/a2(IV) chains, and HPG; type I collagen was also present in the central part of the mesangial areas. This study shows that each glomerular lesion is characterized by particular alterations of the matrix components