CD59 protects rat kidney from complement mediated injury in collaboration with crry.
BACKGROUND
As previously reported, the membrane-bound complement regulator at the C3 level (Crry/p65) is important in maintaining normal integrity of the kidney in rats. However, the role of a complement regulator at the C8/9 level (CD59) is not clear, especially when activation of complement occurs at the C3 level. The aim of this work was to elucidate the in vivo role of CD59 under C3 activating conditions.


METHODS
Two monoclonal antibodies, 5I2 and 6D1, were used to suppress the function of Crry and CD59, respectively. In order to activate alternative the pathway of complement, the left kidney was perfused with 5I2 and/or 6D1 and was recirculated.


RESULTS
In the kidneys perfused with 5I2 alone, deposition of C3 and membrane attack complex (MAC) was observed in the peritubular capillaries, vasa recta, and tubular basement membranes. Cast formation, tubular dilation and degeneration, and cellular infiltration were observed at days 1 and 4, and they recovered by day 7. Further suppression of CD59 by 6D1 significantly enhanced the deposition of MAC and worsened the already exacerbated tubulointerstitial injury. These effects of 6D1 were dose dependent. Perfusion with 6D1 alone did not induce histologic damage or MAC deposition in the tubulointerstitium.


CONCLUSIONS
In rats, CD59 maintains normal integrity of the kidney in collaboration with Crry in rats against complement-mediated damage in vivo.
Watanabe
M
M
Internal Medicine III, Nagoya University School of Medicine, Nagoya, Japan.
Morita
Y
Y
Mizuno
M
M
Nishikawa
K
K
Yuzawa
Y
Y
Hotta
N
N
Morgan
B P
BP
Okada
N
N
Okada
H
H
Matsuo
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface; D018957:CD59 Antigens / Q000276:immunology / Q000378:metabolism*; D002196:Capillaries / Q000276:immunology / Q000378:metabolism; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism*; D003185:Complement C8 / Q000276:immunology / Q000378:metabolism; D003186:Complement C9 / Q000276:immunology / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000276:immunology / Q000378:metabolism; D006417:Hematuria / Q000276:immunology / Q000378:metabolism; D007668:Kidney / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D009500:Neutralization Tests; D011507:Proteinuria / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018957:CD59 Antigens; D003176:Complement C3; D003185:Complement C8; D003186:Complement C9; D015938:Complement Membrane Attack Complex; C513105:Cr1l protein, rat; D011956:Receptors, Cell Surface; D011951:Receptors, Complement