Chemokine receptor (CCR5) expression in human kidneys and in the HIV infected macaque
Chemokine receptor (CCR5) expression in human kidneys and in the HIV infected macaque
复制标题
DOI：
10.1046/j.1523-1755.1998.00211.x
复制
发表时间：
1998-12-01
影响因子：
19.6
通讯作者：
Alpers, CE
中科院分区：
文献类型：
--
作者：
Eitner, F;Cui, Y;Alpers, CE
背景。趋化因子受体 CCR5 已被确定为 CD4 的重要辅助受体，它允许人类免疫缺陷病毒 (HIV) 进入哺乳动物细胞。该受体还可能通过在炎症期间与局部释放的趋化因子（如 RANTES、MIP-1 α 和 MIP-1 β）结合来介导白细胞和实质对损伤的反应。 CCR5 在人类或灵长类动物肾脏中的定位尚不清楚。在本研究中，我们试图通过编码该肽的 mRNA 定位来识别 CCR5 合成位点。方法。克隆到表达载体中的 CCR5 cDNA 被转录成 1.1 Kb 反义核糖核酸探针，用于原位杂交 (ISH) 和 Northern 印迹研究。结果。 Northern 分析表明，从具有严重移植排斥特征的同种异体移植肾切除组织以及患有局灶性间质性肾炎的肾组织中分离出的总 RNA 中 CCR5 mRNA 呈阳性杂交。对于未受疾病影响的人肾组织没有获得可比较的杂交信号。在正常人 (N = 6)、正常猕猴肾脏 (N = 5)、已感染 HIV-2 的猕猴肾脏 (N = 9)、感染 HIV-1 的猕猴肾脏 (N = 4) 和感染 SIV 的猕猴肾脏 (N = 5) 中，通过 ISH 未在固有肾细胞类型中鉴定出 CCR5 mRNA。通过 ISH 在具有间质性肾炎特征的人类肾脏 (N = 3) 和排斥的人类同种异体移植肾 (N = 14) 中鉴定出 CCR5。 CCR5的表达分别限于慢性肾小管间质损伤部位以及血管和间质排斥部位的浸润单核白细胞。结论。了解 CCR5 以及其他趋化因子受体的定位可能有助于我们了解白细胞运输的特异性如何在同种异体移植排斥和间质性肾炎等肾脏炎症过程中实现。他们提供了额外的证据表明趋化因子可能是肾同种异体移植排斥反应中白细胞运输的关键介质。这些发现可能部分解释了在人类艾滋病毒感染中证明肾细胞的艾滋病毒感染的困难，因为这些细胞似乎缺乏病毒进入所需的必需辅助受体的组成型表达。
Background. The chemokine receptor, CCR5, has been identified as an essential co-receptor with CD4, which permits entry of human immunodeficiency virus (HIV) into mammalian cells. This receptor may also mediate leukocyte and parenchymal responses to injury by virtue of its binding to locally released chemokines such as RANTES, MIP-1 alpha and MIP-1 beta during inflammation. The localization of CCR5 in human or primate kidney is unknown. In this study we sought to identify sites of CCR5 synthesis through localization of mRNA coding for this peptide.Methods. CCR5 cDNA cloned into an expression vector was transcribed into a 1.1 Kb antisense riboprobe that was utilized for in situ hybridization (ISH) and Northern blotting studies.Results. Northern analysis demonstrated positive hybridization for CCR5 mRNA in total RNA isolated from allograft nephrectomy tissue with features of severe transplant rejection as well as in kidney tissue with focal interstitial nephritis. No comparable hybridization signal was achieved with human kidney tissue uninvolved by disease. CCR5 mRNA was not identified in intrinsic renal cell types by ISH in normal human (N = 6), normal macaque kidney (N = 5), in kidneys from macaques with established infection by HIV-2 (N = 9), kidneys from macaques infected with HIV-1 (N = 4), nor in kidneys from SIV-infected macaques (N = 5). CCR5 was identified by ISH in human kidneys with features of interstitial nephritis (N = 3) and in rejected human allograft kidneys (N = 14). The expression of CCR5 was restricted to infiltrating mononuclear leukocytes at sites of chronic tubulointerstitial injury and at sites of vascular and interstitial rejection, respectively.Conclusions. Understanding the localization of CCR5 as well as other chemokine receptors may help us understand how specificity in leukocyte trafficking is achieved in renal inflammatory processes such as allograft rejection and interstitial nephritis. They provide additional evidence that chemokines may be critical mediators of leukocyte trafficking in renal allograft rejection. These findings may account in part for the difficulty in demonstrating HIV infection of renal cells in human HIV infection, since these cells appear to lack constitutive expression of an essential co-receptor needed for viral entry.