TY - JOUR
T1 - CD59 protects rat kidney from complement mediated injury in collaboration with Crry
AU - Watanabe, Midoriko
AU - Morita, Yoshiki
AU - Mizuno, Masashi
AU - Nishikawa, Kazuhiro
AU - Yuzawa, Yukio
AU - Hotta, Nigishi
AU - Morgan, B. Paul
AU - Okada, Noriko
AU - Okada, Hidechika
AU - Matsuo, Seiichi
N1 - Funding Information:
Part of this work was supported by the 1999 Grant-in-Aid for Scientific Research from Ministry of Education and Culture of the Japanese government (No. 11671033). The authors appreciate the excellent technical assistance of N. Suzuki, N. Asano, T. Katahara, and Y. Fujitani.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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U2 - 10.1046/j.1523-1755.2000.00318.x
DO - 10.1046/j.1523-1755.2000.00318.x
M3 - Article
C2 - 11012891
AN - SCOPUS:0033797265
SN - 0085-2538
VL - 58
SP - 1569
EP - 1579
JO - Kidney International
JF - Kidney International
IS - 4
ER -