Heterogeneous distribution of monomeric elements from the globular domain (NC1) of type IV collagen in renal basement membranes as revealed by high resolution quantitative immunocytochemistry

Abstract

Heterogeneity in the distribution of major components, namely laminin, entactin/nidogen, heparan sulfate proteoglycan and type IV collagen among renal basement membranes, was previously demonstrated (Desjardins and Bendayan, J Histochem Cytochem 37:885-897, 1989). To further investigate the nature of basement membranes, we applied high resolution immunocytochemistry to reveal monomers M1, M2* and M3 composing the NC1 domain of type IV collagen of various rat renal basement membranes. Labeling for the three monomers was confined to basement membranes. Quantitative morphometrical analysis demonstrated that the labeling for each monomer was not evenly distributed among the various basement membranes. Labeling for M1 was intense over the proximal tubule and the Bowman's capsule basement membranes. In the glomerulus, the mesangial matrix was highly labeled, whereas the glomerular basement membrane was labeled with a lower intensity. In contrast, labeling for M2* and M3 were high in the glomerular basement membrane, while very low in the mesangial matrix. Labeling intensities were intermediate in the other renal basement membranes. The ultrastructural distribution analysis made over the glomerular basement membrane showed a preferential subendothelial localization of M1 monomers. M2 and M3 on the other hand, were found throughout the entire thickness of the basement membrane. M1 monomers being associated to alpha 1(IV) and alpha 2(IV) chains of type IV collagen, and M2* and M3 to alpha 3(IV) and alpha 4(IV) chains respectively, our results thus demonstrate the existence of an heterogeneity in the collagenous nature of renal basement membranes, particularly the glomerular one. This heterogeneity must reflect variations in the structural arrangement of basement membranes and therefore in their functional properties.