Chemokine receptor CCR5 and CXCR4 expression in HIV-associated kidney disease
Chemokine receptor CCR5 and CXCR4 expression in HIV-associated kidney disease
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DOI：
10.1681/asn.v115856
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发表时间：
2000-05-01
影响因子：
13.6
通讯作者：
Alpers, CE
中科院分区：
文献类型：
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作者：
Eitner, F;Cui, Y;Alpers, CE
趋化因子受体CCR5和CXCR4已被确定为HIV-1菌株进入易感细胞的必需辅受体。肾实质细胞的直接感染与hiv相关肾脏疾病的发病机制有关，尽管数据相互矛盾。CCR5和CXCR4在hiv相关肾病患者肾脏中的定位尚不清楚。本研究分析了来自hiv相关肾病（HIVAN） （n = 13）、hiv相关免疫复合物肾小球肾炎（n = 3）、hiv相关血栓性微血管病（n = 1）和hiv阴性肾小球塌陷患者（n = 8）的福尔马林固定、石蜡包埋肾活检。通过免疫组织化学和原位杂交鉴定CCR5和CXCR4的细胞表达位点。通过免疫组织化学和原位杂交检测HIV-1的存在。在所有分析的病例中，趋化因子受体CCR5和CXCR4在肾小球、小管和肾血管细胞中均未检测到。在存在小管间质炎症的情况下，CCR5和CXCR4的表达局限于浸润的单核白细胞。在所有hiv相关肾脏疾病病例中，免疫组织化学检测不到HIV-1蛋白。HIV-1 RNA在一例hiv - van中被鉴定出来，但仅限于浸润白细胞。在所有分析的病例中，内在肾细胞中未检测到HIV-1 RNA。鉴定HIV共受体CCR5和CXCR4的细胞表达可能有助于澄清哪些组织允许直接感染HIV。这些数据不支持产性HIV-1感染肾实质细胞在hiv相关肾病发病机制中的作用。
The chemokine receptors CCR5 and CXCR4 have been identified as essential coreceptors for entry of HIV-1 strains into susceptible cells. Direct infection of renal parenchymal cells has been implicated in the pathogenesis of HIV-associated renal disease, although data are conflicting. The localization of CCR5 and CXCR4 in kidneys with HIV-associated renal disease is unknown. Formalin-fixed, paraffin-embedded renal biopsies from patients with HIV-associated nephropathy (HIVAN) (n = 13), HIV-associated immune complex glomerulonephritis (n = 3), HIV-associated thrombotic microangiopathy (n = 1), and HIV-negative patients with collapsing glomerulopathy (n = 8) were analyzed in this study. Cellular sites of expression of CCR5 and CXCR4 were identified by immunohistochemistry and by in situ hybridization. The presence of HIV-1 was detected by immunohistochemistry and by in situ hybridization. Expression of both chemokine receptors CCR5 and CXCR4 was undetectable in intrinsic glomerular, tubular, and renovascular cells in all analyzed cases. In the presence of tubulointerstitial inflammation, CCR5 and CXCR4 expression was localized to infiltrating mononuclear leukocytes. HIV-1 protein was undetectable by immunohistochemistry in ail cases of HIV-associated renal disease. HIV-1 RNA was identified in one case of HIVAN but was restricted to infiltrating leukocytes. HIV-1 RNA was not detected in intrinsic renal cells in all analyzed cases. Identifying the cellular expression of HIV-coreceptors CCR5 and CXCR4 may help to clarify which tissues are permissive for direct HIV infection. These data do not support a role of productive HIV-1 infection of renal parenchymal cells in the pathogenesis of HIV-associated renal disease.