Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL/lpr mice
Fc receptor-independent development of autoimmune glomerulonephritis in lupus-prone MRL/lpr mice
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DOI：
10.1002/art.10813
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发表时间：
2003-02-01
影响因子：
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通讯作者：
Saito, T
中科院分区：
文献类型：
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作者：
Matsumoto, K;Watanabe, N;Saito, T
Objective.为了确定Fc受体（FcR）在MRL/lpr小鼠（最广泛使用的狼疮易感小鼠模型之一）中自身免疫性GN和血管炎的发展中的作用，FcR在抗体和免疫复合物介导的炎症和自身免疫（包括肾小球肾炎（GN））中起关键作用。通过回交8代产生FcR γ（-/-）MRL/lpr小鼠。对肾脏、肺和皮肤中GN和各种大小血管的血管炎的发展进行组织病理学分析。在16-24周龄时生化测定自身抗体和免疫复合物水平，并与FcR γ（+）MRL/lpr小鼠中的结果进行比较。同时记录小鼠的寿命。FcR γ（-/-）和FcR γ（+）MRL/lpr小鼠均出现弥漫性增生性GN，伴IgG和C3沉积。FcRgamma（+）和FcRgamma（-/-）MRL/lpr小鼠的存活率和蛋白尿程度无差异。无论FcR表达水平如何，两种小鼠之间的血清IgG、抗DNA抗体或循环免疫复合物水平均无显著差异。在FcRgamma（+）和FcRgamma（-/-）MRL/lpr小鼠中均观察到肾脏和肺中型动脉中的坏死性血管炎以及皮肤中的小血管炎。与此相反，在FcR γ（+）MRL/lpr小鼠中诱导Arthus反应，而在FcR γ（-/-）MRL/lpr小鼠中不诱导Arthus反应。与（NZB X NZW）F-1（另一种狼疮易感小鼠品系，以FcR依赖性方式发展GN）不同，MRL/lpr小鼠中自身免疫性GN和血管炎的发展是FcR非依赖性的，这意味着FcR对自身免疫性疾病发展的贡献具有异质性。
Objective. To determine the role of Fc receptors (FcR), which play crucial roles in antibody and immune complex-mediated inflammation and autoimmunity, including glomerulonephritis (GN), in the development of autoimmune GN and vasculitis in MRL/lpr mice, one of the most widely used lupus-prone mouse models.Methods. FcRgamma(-/-) MRL/lpr mice were generated by backcrossing for 8 generations. The development of GN and vasculitis of various sized vessels was analyzed histopathologically in the kidney, lung, and skin. Autoantibody and immune complex levels were determined biochemically at 16-24 weeks of age and compared with the findings in FcRgamma(+) MRL/lpr mice. The lifespan of the mice was also recorded.Results. Diffuse proliferative GN, with deposition of IgG and C3, developed in both FcRgamma(-/-) and FcRgamma(+) MRL/lpr mice. There was no difference in the survival rate and degree of proteinuria between FcRgamma(+) and FcRgamma(-/-) MRL/lpr mice. Regardless of the level of FcR expression, there were no significant differences in the levels of serum IgG, anti-DNA antibody, or circulating immune complexes between the two types of mice. Necrotizing vasculitis in medium-sized arteries of the kidneys and lungs as well as small-vessel vasculitis in the skin was observed in both in FcRgamma(+) and FcRgamma(-/-) MRL/lpr mice. In contrast, the Arthus reaction was induced in FcRgamma(+) MRL/lpr mice, but not in FcRgamma(-/-) MRL/lpr mice.Conclusion. Unlike (NZB X NZW)F-1, the other strain of lupus-prone mice that develops GN in an FcR-dependent manner, the development of autoimmune GN and vasculitis in MRL/lpr mice was FcR-independent, implying heterogeneity of the contribution of FcR to the development of autoimmune disease.