Quantitative studies of tubular immune complex formation and clearance in rats

Abstract

Tubular antibody deposition and clearance was quantitatively studied using affinity-purified rabbit antibodies to rat Tamm-Horsfall protein (TH), a surface membrane glycoprotein of the tubular cells of the thick ascending limb of the loop of Henle. Immune complexes are formed in situ at the base of these cells in rats injected with antisera to TH. The renal binding of I125-anti-TH was determined in pair label studies. Kidneys and other organs were removed from groups of rats for isotope counting at four hours to 14 days after an injection of I125-anti-TH and I131-normal rabbit IgG. The greatest total renal anti-TH binding after injection of 500 micrograms of anti-TH was observed at 24 hours in normal rats (18.55 +/- 1.6 micrograms). During the period of most rapid clearance (day 2 to day 7) the half life of renal anti-TH binding (84.2 hours) and the half life of anti-TH in the serum (68.5 hours) were shorter than that of IgG in the serum (117.8 hours). There was no substantial uptake of anti-TH by other organs. A close relationship between serum levels and renal uptake of anti-TH at 24 hours was also observed in rats given from 50 to 6000 micrograms of anti-TH; renal saturation was evident only at the highest dose. This close relationship was also present during the clearance phase in rats injected with 3700 micrograms of anti-TH; the half life of anti-TH was 96.2 hours in kidneys and 110 hours in serum while the half life of rabbit IgG in serum was 151.8 hours. Markedly increased renal uptake of anti-TH was observed in protein-uric rats with passive Heymann nephritis. In very proteinuric rats, 14.1% of the injected dose was bound to kidneys at 24 hours. In these rats, serum anti-TH levels decreased very rapidly to 4% of control serum levels by five days. Throughout the period of study, the serum levels of anti-TH determined by direct radiometric assay corresponded very closely to those obtained by enzyme-linked immunosorbent assay (ELISA). Urinary excretion was a major mechanism for the clearance of anti-TH in proteinuric rats; more than 10% of the injected I125-anti-TH was recovered intact (that is, protein bound) during the first day after injection. During the clearance phase for renal deposits, urinary clearance of anti-TH exceeded urinary clearance of IgG due to release of renal bound antibody into urine.(ABSTRACT TRUNCATED AT 400 WORDS)