Influence of altered glomerular permeability on renal tubular immune complex formation and clearance.

Proteinuria was induced in rats to determine whether intravenously injected antibodies to a distal tubular antigen would bind to the luminal surfaces of distal tubular cells in vivo. Rats with proteinuria induced by an intravenous injection of sheep antisera to Fx1A (passive Heymann model) were injected 10 days later with rabbit antisera to Tamm-Horsfall protein. Linear rabbit IgG deposits along the luminal cell surfaces in the initial portion of the thick ascending limb of the loop of Henle (ALH) were demonstrated by immunofluorescence microscopy at 4 hours and were maximal 1 to 3 days after injection of antibodies to Tamm-Horsfall protein. The distance that these immune deposits extended along the ALH was directly proportional to the magnitude of proteinuria. Light microscopy showed periodic acid-Schiff-positive luminal deposits and an increased number of mitoses confined to the early ALH. Ultrastructural studies revealed continuous very electron-dense deposits initially covering the luminal surfaces of ALH cells. During the clearance phase, these deposits were surrounded and separated from ALH cell surfaces by a less electron-dense fibrillar material with the ultrastructural characteristics of Tamm-Horsfall protein. The mechanism of immune complex formation in the present study appears to involve the in situ combination of rabbit antibodies to Tamm-Horsfall protein in the glomerular filtrate with a tubular surface membrane antigen, Tamm-Horsfall protein.