Renal F4/80+CD11c+ Mononuclear Phagocytes Display Phenotypic and Functional Characteristics of Macrophages in Health and in Adriamycin Nephropathy
Renal F4/80+CD11c+ Mononuclear Phagocytes Display Phenotypic and Functional Characteristics of Macrophages in Health and in Adriamycin Nephropathy
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DOI：
10.1681/asn.2013121336
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发表时间：
2015-02-01
影响因子：
13.6
通讯作者：
Harris, David C. H.
中科院分区：
文献类型：
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作者：
Cao, Qi;Wang, Yiping;Harris, David C. H.
巨噬细胞(M Phi S)和树突状细胞(DC)的传统标记缺乏特异性，经常重叠，导致对这些细胞在肾脏和其他疾病中的确切功能的混淆和争议。本研究旨在鉴定同时表达M phi S和DC关键标志的肾脏单核巨噬细胞(RMP)的表型和功能。F4/80(+)CD11c(+)细胞占正常肾脏和阿霉素肾病(AN)小鼠总RMP的45%。尽管表达DC标志物CD11c，但这些双阳性RMP具有M Phi样形态特征，高表达CD68、CD204和CD206，高吞噬能力但低抗原提呈能力。F4/80(+)CD11c(+)细胞仅见于肾皮质，髓质未见。在AN中，F4/80CD11c细胞表现为高表达炎症介质和共刺激因子的M1 M phi表型。过继转移F4/80(+)CD11c(+)细胞可加重小鼠肾脏损伤。此外，对普通祖细胞的过继转移显示，肾脏F4/80(+)CD11c(+)细胞主要来自单核细胞，而不是DC前体源。总之，肾脏F4/80(+)CD11c(+)细胞是RMPS的一个主要亚群，在健康和AN患者中表现出M Phi样的表型和功能特征。
Conventional markers of macrophages (M phi s) and dendritic cells (DCs) lack specificity and often overlap, leading to confusion and controversy regarding the precise function of these cells in kidney and other diseases. This study aimed to identify the phenotype and function of renal mononuclear phagocytes (rMPs) expressing key markers of both M phi s and DCs. F4/80(+)CD11c(+) cells accounted for 45% of total rMPs in normal kidneys and in those from mice with Adriamycin nephropathy (AN). Despite expression of the DC marker CD11c, these double-positive rMPs displayed the features of M phi s, including M phi-like morphology, high expression of CD68, CD204, and CD206, and high phagocytic ability but low antigen-presenting ability. F4/80(+)CD11c(+) cells were found in the cortex but not in the medulla of the kidney. In AN, F4/80 CD11c cells displayed an M1 M phi phenotype with high expression of inflammatory mediators and costimulatory factors. Adoptive transfer of F4/80(+)CD11c(+) cells separated from diseased kidney aggravated renal injury in AN mice. Furthermore, adoptive transfer of common progenitors revealed that kidney F4/80(+)CD11c(+) cells were derived predominantly from monocytes, but not from pre-DCs. In conclusion, renal F4/80(+)CD11c(+) cells are a major subset of rMPs and display M phi-like phenotypic and functional characteristics in health and in AN.