Tubulointerstitial injury induced in rats by a monoclonal antibody that inhibits function of a membrane inhibitor of complement.
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 suppress functions of rat membrane inhibitors of complement, two mAbs, 512 and 6D1, were used. 5I2 and 6D1 inhibit functions of membrane inhibitors of complement at C3 level (rat Crry/p65) and C8/9 level (rat CD59), respectively. F(ab')2 fragment of 5I2 or 6D1 was perfused in the left kidneys, and perfusate was discarded from the renal vein. After perfusion, 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 perfusion with 5I2, cast formation, dilatation of tubular lumen, and tubular cell degeneration were observed. At day 4 through day 7, significant mononuclear 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 areas as 5I2, but C3 or C5b-9 deposition was not observed. Rats perfused with 6D1 or vehicle only did not show any pathology in the left kidneys. These results suggest that rat Crry/p65 plays protective roles against 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.
Nomura
A
A
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Nishikawa
K
K
Yuzawa
Y
Y
Okada
H
H
Okada
N
N
Morgan
B P
BP
Piddlesden
S J
SJ
Nadai
M
M
Hasegawa
T
T
Matsuo
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003176:Complement C3 / Q000032:analysis / Q000276:immunology*; D003169:Complement Inactivator Proteins / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007684:Kidney Tubules / Q000276:immunology / Q000473:pathology; D051379:Mice; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D003176:Complement C3; D003169:Complement Inactivator Proteins; D007074:Immunoglobulin G