Kidney immunopathology and pathophysiology in rats immunized with proximal tubule cell brush border or basolateral...

Proximal tubule pathology in Heymann nephritis has been attributed to anti-brush border antibodies, but antibodies with other specificities might also be important. To determine whether injury to the basolateral membranes of proximal tubules could occur independently of brush border injury, LEW rats were immunized either with partially purified basolateral or brush border membrane vesicles. Both immunogens produced glomerular immunopathology and pathophysiology identical in magnitude and time course to that seen in Heymann nephritis. Antibodies eluted from the kidneys of rats immunized with either antigen preparation stained the brush border in vitro. However, circulating anti-brush border antibodies were in significant titers only in rats immunized with brush border vesicles, whereas antibodies that stained the cytoplasm of both proximal and distal tubules predominated in rats immunized with basolateral membranes. With the onset of proteinuria, rats immunized with brush border membranes developed the proximal tubule pathology of Heymann nephritis. In rats immunized with basolateral membranes, the brush border and apical aspect of proximal tubule cells remained essentially normal. However, defects of basolateral membrane transport function were present, indicating that those defects need not necessarily be secondary to brush border damage. The dissociation of brush border damage from glomerular injury suggests that different antibody populations may account for each. Furthermore, anti-brush border antibodies may not account for all aspects of proximal tubule pathology in Heymann nephritis.