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Binding of bacterial adhesins to rat glomerular mesangium in vivo . Two well characterized bacterial adhesins, the O75X fimbriae of Escherichia coli and the type-3 fimbriae of Klebsiellae , with in vitro affinities to type IV and V collagens, respectively, were used to test whether bacterial components with affinity for glomerular matrix could bind to glomeruli in vivo . The purified fimbrial proteins were injected into rats, and kidney samples were studied by immunofluorescence at two hours to nine months postinjection. The O75X, but not the type-3 fimbriae, formed mesangial deposits that persisted for months. Preincubation of the O75X fimbriae with type IV collagen significantly reduced the glomerular binding. The fimbrial deposits were extracellular, as anti-O75X IgG injected into rats bound to glomeruli. Proteinuria or histological damage could not be detected even after passive or active immunizations of the rats. The results demonstrate that bacterial adhesins may bind in vivo to and persist in glomeruli by their specific affinities. The results also indicate that additional factors provided by the bacteria or the host are needed for glomerular damage to take place.

We describe here the size and location of nephrin, the first protein to be identified at the glomerular podocyte slit diaphragm. In Western blots, nephrin antibodies generated against the two terminal extracellular Ig domains of recombinant human nephrin recognized a 180-kDa protein in lysates of human glomeruli and a 150-kDa protein in transfected COS-7 cell lysates. In immunofluorescence, antibodies to this transmembrane protein revealed reactivity in the glomerular basement membrane region, whereas the podocyte cell bodies remained negative. In immunogold-stained thin sections, nephrin label was found at the slit between podocyte foot processes. The congenital nephrotic syndrome of the Finnish type (NPHS1), a disease in which the nephrin gene is mutated, is characterized by massive proteinuria alreadyin uteroand lack of slit diaphragm and foot processes. These features, together with the now demonstrated localization of nephrin to the slit diaphragm area, suggests an essential role for this protein in the normal glomerular filtration barrier. A zipper-like model for nephrin assembly in the slit diaphragm is discussed, based on the present and previous data.