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Notch1诱导的小鼠T细胞急性淋巴细胞白血病中腹膜白血病相关巨噬细胞的特征分析

Characterization of peritoneal leukemia-associated macrophages in Notch1-induced mouse T cell acute lymphoblastic leukemia.

作者信息

Chen Shayan, Yang Xiao, Feng Wenli, Yang Feifei, Wang Rong, Chen Chong, Wang Lina, Lin Yongmin, Ren Qian, Zheng Guoguang

机构信息

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China; Department of Laboratory Science, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine (Nankai Hospital), Nankai District, Tianjin 300100, China.

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

出版信息

Mol Immunol. 2017 Jan;81:35-41. doi: 10.1016/j.molimm.2016.11.014. Epub 2016 Nov 23.

Abstract

Macrophages, which have remarkable plasticity, are indispensable cellular components and play essential roles in both innate and adaptive immune responses. Peritoneal macrophages show unique gene expression profile and peritoneal cavity is also involved in leukemia. However, the characteristics of peritoneal leukemia-associated macrophages (Per LAMs) have not been established. Here we studied the phenotype of Per LAMs, their subpopulations in Notch1-induced acute lymphoblastic leukemia mice and compared with LAMs from BM or spleen in the same model. Peritoneal macrophages and Per LAMs simultaneously expressed high level iNOS and Arg1, which was not commonly observed in macrophages from different origins. Furthermore, LAMs from peritoneal, BM and spleen expressed lower level CSF-1, TGF-β1 and VEGF-A than tumor-associated macrophages (TAMs). Moreover, diverse responses in the expression of some phenotype-associated genes to leukemia microenvironments were detected among those LAMs. In addition, Per LAMs can be sub-divided into CD206 and CD206 sub-populations, which expressed both M1- and M2-associated genes. These results revealed the unique phenotype of Per macrophages and Per LAMs and contributed to better understanding of macrophage plasticity and their pathological roles in leukemia.

摘要

巨噬细胞具有显著的可塑性,是不可或缺的细胞成分,在固有免疫和适应性免疫反应中均发挥着重要作用。腹膜巨噬细胞表现出独特的基因表达谱,且腹膜腔也与白血病有关。然而,腹膜白血病相关巨噬细胞(Per LAMs)的特征尚未明确。在此,我们研究了Per LAMs的表型、它们在Notch1诱导的急性淋巴细胞白血病小鼠中的亚群,并与同一模型中来自骨髓或脾脏的LAMs进行了比较。腹膜巨噬细胞和Per LAMs同时高水平表达诱导型一氧化氮合酶(iNOS)和精氨酸酶1(Arg1),这在不同来源的巨噬细胞中并不常见。此外,来自腹膜、骨髓和脾脏的LAMs表达的集落刺激因子-1(CSF-1)、转化生长因子-β1(TGF-β1)和血管内皮生长因子-A(VEGF-A)水平低于肿瘤相关巨噬细胞(TAMs)。此外,在这些LAMs中检测到一些表型相关基因的表达对白血病微环境有不同反应。此外,Per LAMs可分为CD206和CD206亚群,它们同时表达与M1和M2相关的基因。这些结果揭示了腹膜巨噬细胞和Per LAMs的独特表型,有助于更好地理解巨噬细胞的可塑性及其在白血病中的病理作用。

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