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健康小鼠肾脏及实验性肾小球肾炎中树突状细胞的鉴定与功能特性研究

Identification and functional characterization of dendritic cells in the healthy murine kidney and in experimental glomerulonephritis.

作者信息

Krüger Thilo, Benke Dirk, Eitner Frank, Lang Andreas, Wirtz Monika, Hamilton-Williams Emma E, Engel Daniel, Giese Bernd, Müller-Newen Gerhard, Floege Jürgen, Kurts Christian

机构信息

Department of Nephrology and Clinical Immunology, University Clinic of Aachen, Aachen, Germany.

出版信息

J Am Soc Nephrol. 2004 Mar;15(3):613-21. doi: 10.1097/01.asn.0000114553.36258.91.

Abstract

The kidney tubulointerstitium contains numerous bone marrow-derived antigen-presenting cells, which are often referred to as resident tissue macrophages, although several previous studies had demonstrated characteristics of dendritic cells (DC). In this study, we describe a subset of tubulointerstitial cells expressing the DC marker CD11c. A protocol was established to isolate these cells for in vitro analysis. Renal CD11c(+) cells resembled splenic DC, but not peritoneal macrophages, in morphology, lysosomal content, phagocytic activity, microbicidal effector functions, expression of T cell costimulatory molecules, and ability to activate T cells. Nevertheless, many CD11c(+) renal cells expressed low or intermediate levels of F4/80 and CD11b, indicating that both markers are not absolutely specific for macrophages in the kidney. Subpopulations of renal DC could be distinguished based on their expression of MHC class II and costimulatory molecules and may represent different maturation stages. In nephrotoxic glomerulonephritis, increased numbers of CD11c(+) cells showing DC functionality were found in the tubulointerstitium. Focal accumulation was seen within tubulointerstitial mononuclear infiltrates and adjacent to, but not within, inflamed glomeruli. These results are the first to identify and characterize renal CD11c(+) cells as DC and to demonstrate marked changes in experimental glomerulonephritis.

摘要

肾小管间质包含大量源自骨髓的抗原呈递细胞,这些细胞通常被称为驻留组织巨噬细胞,尽管此前有多项研究显示其具有树突状细胞(DC)的特征。在本研究中,我们描述了表达DC标志物CD11c的肾小管间质细胞亚群。我们建立了一种方案来分离这些细胞用于体外分析。肾CD11c(+)细胞在形态、溶酶体含量、吞噬活性、杀菌效应功能、T细胞共刺激分子的表达以及激活T细胞的能力方面类似于脾DC,而不像腹膜巨噬细胞。然而,许多CD11c(+)肾细胞表达低水平或中等水平的F4/80和CD11b,这表明这两种标志物对肾巨噬细胞并非绝对特异。肾DC亚群可根据其MHC II类分子和共刺激分子的表达来区分,可能代表不同的成熟阶段。在肾毒性肾小球肾炎中,在肾小管间质中发现显示DC功能的CD11c(+)细胞数量增加。在肾小管间质单核细胞浸润内以及与炎症肾小球相邻但不在其中的部位可见局灶性聚集。这些结果首次将肾CD11c(+)细胞鉴定并表征为DC,并证明了实验性肾小球肾炎中的显著变化。

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