High levels of complement C3a receptor in the glomeruli in lupus nephritis
High levels of complement C3a receptor in the glomeruli in lupus nephritis
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DOI：
10.1053/j.ajkd.2007.02.271
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发表时间：
2007-05-01
影响因子：
13.2
通讯作者：
Matsuo, Seiichi
中科院分区：
文献类型：
--
作者：
Mizuno, Masashi;Blanchin, Stephanie;Matsuo, Seiichi
背景：考虑到补体系统在肾脏疾病中的关键作用，我们在体外和原位研究了人类补体C3a受体（C3aR）的分子和细胞特性，并观察了其在几种人类肾脏病理状态中的表达。方法：制备几种抗体，并进行免疫组化和Western blot分析，研究C3aR在髓系和非髓系细胞系上的体外表达及其调控。此外，研究了C3aR在对照组肾切除术肾脏和116例肾脏疾病患者（包括狼疮肾炎（狼疮- n））的活检标本中的分布。结果：C3aR是一种高度n -糖基化的蛋白，表观分子质量为65 ~ 95kd，在髓细胞和内皮细胞中表达。C3aR在干扰素γ治疗下特别上调，但不受其他炎症细胞因子的影响，如肿瘤坏死因子和转化生长因子。正常人肾未见C3aR染色。然而，在42.9%的狼疮n标本中检测到肾小球C3aR染色，与免疫球蛋白G免疫复合物沉积有关。染色强度与疾病严重程度相关。81.3%的世界卫生组织IV类活动性病变样本在内皮区发现C3aR。相反，在其他肾脏疾病患者的肾脏中，免疫组织化学未检测到C3aR。结论：我们的数据表明，C3aR的表达在某些疾病条件下受到严格调控和改变。C3aR可作为狼疮n患者诊断和疾病活动性的独特生物标志物。
Background: Taking into consideration the key role of the complement system in renal diseases, we investigated molecular and cellular properties of the human complement C3a receptor (C3aR) in vitro and in situ, looking at its expression in several human renal pathological states.Methods: Several antibodies were generated and used for immunohistochemistry and Western blot analyses to address C3aR expression and its regulation in vitro on cell lines of myeloid cells and nonmyeloid cell lineages. Furthermore, C3aR distribution was investigated in control nephrectomized kidneys and 116 biopsy specimens from patients with renal diseases, including lupus nephritis (lupus-N).Results: C3aR is a highly N-glycosylated protein with an apparent molecular mass of 65 to 95 kd expressed by myeloid and endothelial cells. C3aR is particularly upregulated in response to interferon gamma treatment, but was unaffected by the other inflammatory cytokines, such as tumor necrosis factor alpha and transforming growth factor beta. In normal human kidney, C3aR staining was not observed. However, glomerular C3aR staining was detected in 42.9% of lupus-N specimens in association with immunoglobulin G immune-complex depositions. Staining intensity correlated with disease severity. C3aR was found in the endothelial area of 81.3% of samples classified as World Health Organization class IV with active lesions. Conversely, C3aR was not detected by means of immunohistochemistry in kidneys from patients with other renal diseases.Conclusion: Our data indicate that C3aR expression is tightly regulated and altered in certain disease conditions. C3aR may be used as a unique biomarker of diagnosis and disease activity in patients with lupus-N.