TUBULOINTERSTITIAL INJURY-INDUCED IN RATS BY A MONOCLONAL-ANTIBODY THAT INHIBITS FUNCTION OF A MEMBRANE INHIBITOR OF COMPLEMENT

Citation
A. Nomura et al., TUBULOINTERSTITIAL INJURY-INDUCED IN RATS BY A MONOCLONAL-ANTIBODY THAT INHIBITS FUNCTION OF A MEMBRANE INHIBITOR OF COMPLEMENT, The Journal of clinical investigation, 96(5), 1995, pp. 2348-2356
Citations number
36
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
00219738
Volume
96
Issue
5
Year of publication
1995
Pages
2348 - 2356
Database
ISI
SICI code
0021-9738(1995)96:5<2348:TIIRBA>2.0.ZU;2-V
Abstract
The kidney widely expresses membrane-associated complement regulatory proteins (membrane inhibitors of complement). The aim of this work was to evaluate the roles of these molecules in rat kidneys in vivo. To s uppress functions of rat membrane inhibitors of complement, two mAbs, 5I2 and 6D1, were used, 5I2 and 6D1 inhihit functions of membrane inhi bitors of complement at C3 level (rat Crry/p65) and C8/9 level (rat CD 59), respectively. F(ab')2 fragment of 5I2 or 6D1 was perfused in the left kidneys, and perfusate was discarded from the renal vein. After p erfusion, the left kidneys were connected to systemic circulation. In rats perfused with 5I2, mouse IgG was found in glomeruli, peritubular capillaries, vascular bundles, and tubules 15 min after recirculation, Binding of C3 and C5b-9 was evident in these areas, 1 d after perfusi on with 5I2, cast formation, dilatation of tubular lumen, and tubular cell degeneration were observed. At day 4 through day 7, significant m ononuclear cell infiltration and proximal tubule damage were observed. These changes were completely prevented by complement depletion. Rats perfused with 6D1 showed the binding of mouse IgG in the similar area s as 5I2, but C3 or C5b-9 deposition was not observed. Rats perfused w ith 6D1 or vehicle only did not show any pathology in the left kidneys , These results suggest that rat Crry/p65 plays protective roles again st spontaneously occurring indiscriminate attack to tubulointerstitial tissues by autologous complement and that rat Crry/p65 is one of the important factors to maintain normal integrity of the kidney in rats.