权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

PATHOPHYSIOLOGICAL ANALYSIS OF GOODPASTURE SYNDROME USING FcRγ-DEFICIENT MICE

使用 FcRγ 缺陷小鼠对 Goodpasture 综合征进行病理生理学分析

基本信息

批准号：
10670538
负责人：
HASEGAWA Yoshinori
金额：
$ 1.79万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670538/
关键词：
Goodpasture Syndrome Fc receptor Anti-basement membrane antibody Good pasture症候群

项目摘要

Several recent studies have demonstrated the central role of Fe receptor (FcR) rather than the complement system in triggering hypersensitivity reactions including Goodpasture syndrome. We investigated the role of FcR for IgG (FcγR) using a murine model of accelerated anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis and alveolitis as a representative of type II hypersensitivity diseases. Intravenous injection of rabbit anti-GBM antibody after preimmunization with normal rabbit IgG induced proteinuria and azotemia in wild-type C57BL/6 and CD40 +/- mice but not in FeR γ chain (FcRγ) -/- mice, or CD40 -/- mice. Light microscope findings revealed marked tissue damage in the glomeruli of wild-type C57BL/6 and CD40 +/- mice. However, no tissue damage except polymorphonuclear cell infiltration was observed in the glomeruli of FcRγ -/- mice. The glomeruli of CD40 -/- mice were almost normal. Immunohistochemistry revealed the binding of rabbit IgG to the GBM in all mice injected with anti-GBM antibody. However, depositions of mouse IgG and complement to the glomeruli were not observed in CD40 -/- mice, and deposition of fibrin was not observed in FcRγ -/-or CD40 -/- mice. Furthermore, anti-basement membrane antibody-mediated alveolitis was not induced in FcRγ -/- mice. These findings suggest that FcγR may initiate anti-basement membrane antibody-mediated renal and pulmonary disease, that is named as Goodpasture syndrome. We conclude that FcγR rather than the complement system is critically involved in the development of type II hypersensitivity diseases.

最近的几项研究表明，铁受体（FcR），而不是补体系统在引发包括Goodpasture综合征的超敏反应的中心作用。我们使用加速抗肾小球基底膜（GBM）抗体介导的肾小球肾炎和肺泡炎（作为II型超敏反应性疾病的代表）的小鼠模型研究了IgG的Fc受体（FcγR）的作用。用正常兔IgG预免疫后静脉注射兔抗GBM抗体可诱导野生型C57 BL/6和CD 40 +/-小鼠出现蛋白尿和氮质血症，但对Fe R γ链（FcRγ）-/-小鼠和CD 40-/-小鼠无明显影响。光学显微镜检查结果显示，野生型C57 BL/6和CD 40 +/-小鼠的肾小球中存在明显的组织损伤。而FcRγ -/-小鼠肾小球除多形核细胞浸润外，未见组织损伤。CD 40-/-小鼠肾小球基本正常。免疫组织化学显示，在所有注射抗GBM抗体的小鼠中，兔IgG与GBM结合。然而，在CD 40-/-小鼠中未观察到小鼠IgG和补体沉积到肾小球，在FcRγ -/-或CD 40-/-小鼠中未观察到纤维蛋白沉积。此外，在FcRγ -/-小鼠中未诱导抗基底膜抗体介导的肺泡炎。提示FcγR可引起抗基底膜抗体介导的肺、肾疾病，即肺出血肾炎综合征。我们的结论是FcγR而不是补体系统是关键参与了II型超敏反应性疾病的发展。