CD59与Crry协同保护大鼠肾脏免受补体介导的损伤。

CD59 protects rat kidney from complement mediated injury in collaboration with crry.

作者信息

Watanabe M, Morita Y, Mizuno M, Nishikawa K, Yuzawa Y, Hotta N, Morgan B P, Okada N, Okada H, Matsuo S

机构信息

Internal Medicine III, Nagoya University School of Medicine, Nagoya, Japan.

出版信息

Kidney Int. 2000 Oct;58(4):1569-79. doi: 10.1046/j.1523-1755.2000.00318.x.

DOI:10.1046/j.1523-1755.2000.00318.x

PMID:11012891

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.

摘要

背景

如先前报道，C3 水平的膜结合补体调节蛋白（Crry/p65）对维持大鼠肾脏的正常完整性很重要。然而，C8/9 水平的补体调节蛋白（CD59）的作用尚不清楚，尤其是当补体在 C3 水平被激活时。本研究的目的是阐明在 C3 激活条件下 CD59 在体内的作用。

方法

使用两种单克隆抗体 5I2 和 6D1 分别抑制 Crry 和 CD59 的功能。为了激活补体替代途径，用 5I2 和/或 6D1 灌注左肾并进行再循环。

结果

在仅用 5I2 灌注的肾脏中，在肾小管周围毛细血管、直小血管和肾小管基底膜中观察到 C3 和膜攻击复合物（MAC）的沉积。在第 1 天和第 4 天观察到管型形成、肾小管扩张和变性以及细胞浸润，到第 7 天恢复。6D1 对 CD59 的进一步抑制显著增强了 MAC 的沉积，并使已经加剧的肾小管间质损伤恶化。6D1 的这些作用是剂量依赖性的。单独用 6D1 灌注未在肾小管间质中诱导组织学损伤或 MAC 沉积。