Ultrastructural studies of tubulointerstitial immune complex nephritis in rats immunized with Tamm-Horsfall protein

Rats immunized with Tamm-Horsfall protein, a surface membrane glycoprotein of cells of the ascending thick limb of Henle's loop, develop autoantibodies to Tamm-Horsfall protein and a tubulointerstitial nephritis selectively involving the thick ascending limb of Henle's loop. The localization of the immune deposits formed in this model was studied by transmission electron microscopy. The frequency, size, and distribution of electron-dense deposits closely paralleled that of granular and nodular deposits of rat IgG, C3, and Tamm-Horsfall protein at the base of the cells of the ascending thick limb of Henle's loop. The earliest electron-dense deposits were present in the extracellular space between basal infoldings of cell membranes and the tubular basement membranes. In the more advanced lesions, the larger electron-dense deposits were also present within the tubular basement membranes and between tubular cell membranes displacing tubular structures. Selective mononuclear cell infiltration around these tubules with deposits in this model of tubulointerstitial nephritis suggests that antibodies to Tamm-Horsfall protein cross tubular basement membranes and form immune complexes in situ by combining with the Tamm-Horsfall protein molecules of basal cell surface membranes.