CD59 protects rat kidney from complement mediated injury in collaboration with Crry

Midoriko Watanabe, Yoshiki Morita, Masashi Mizuno, Kazuhiro Nishikawa, Yukio Yuzawa, Nigishi Hotta, B. Paul Morgan, Noriko Okada, Hidechika Okada, Seiichi Matsuo

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1569-1579
Number of pages11
JournalKidney International
Volume58
Issue number4
DOIs
Publication statusPublished - 01-01-2000
Externally publishedYes

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Complement Membrane Attack Complex
Kidney
Wounds and Injuries
Alternative Complement Pathway
Complement Activation
Rectum
Basement Membrane
Dilatation
Perfusion
Monoclonal Antibodies
Membranes

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Watanabe, M., Morita, Y., Mizuno, M., Nishikawa, K., Yuzawa, Y., Hotta, N., ... Matsuo, S. (2000). CD59 protects rat kidney from complement mediated injury in collaboration with Crry. Kidney International, 58(4), 1569-1579. https://doi.org/10.1046/j.1523-1755.2000.00318.x
Watanabe, Midoriko ; Morita, Yoshiki ; Mizuno, Masashi ; Nishikawa, Kazuhiro ; Yuzawa, Yukio ; Hotta, Nigishi ; Morgan, B. Paul ; Okada, Noriko ; Okada, Hidechika ; Matsuo, Seiichi. / CD59 protects rat kidney from complement mediated injury in collaboration with Crry. In: Kidney International. 2000 ; Vol. 58, No. 4. pp. 1569-1579.
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abstract = "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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Watanabe, M, Morita, Y, Mizuno, M, Nishikawa, K, Yuzawa, Y, Hotta, N, Morgan, BP, Okada, N, Okada, H & Matsuo, S 2000, 'CD59 protects rat kidney from complement mediated injury in collaboration with Crry', Kidney International, vol. 58, no. 4, pp. 1569-1579. https://doi.org/10.1046/j.1523-1755.2000.00318.x

CD59 protects rat kidney from complement mediated injury in collaboration with Crry. / Watanabe, Midoriko; Morita, Yoshiki; Mizuno, Masashi; Nishikawa, Kazuhiro; Yuzawa, Yukio; Hotta, Nigishi; Morgan, B. Paul; Okada, Noriko; Okada, Hidechika; Matsuo, Seiichi.

In: Kidney International, Vol. 58, No. 4, 01.01.2000, p. 1569-1579.

Research output: Contribution to journalArticle

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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

PY - 2000/1/1

Y1 - 2000/1/1

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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