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树突状细胞与 K562 CML 细胞共培养导致的生物力学改变及其在免疫逃逸中的潜在作用。

Biomechanical alterations of dendritic cells by co-culturing with K562 CML cells and their potential role in immune escape.

机构信息

Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, PR China.

出版信息

J Biomech. 2010 Aug 26;43(12):2339-47. doi: 10.1016/j.jbiomech.2010.04.028.

DOI:10.1016/j.jbiomech.2010.04.028
PMID:20537332
Abstract

Dendritic cells (DCs), which are potent antigen presenting cells (APCs), are utilized to deliver the signals essential for the initiation of immune responses. In this study, we used an interdisciplinary approach to characterize the effect of K562 cells, a human chronic myeloid leukemia (CML) cell line, on the biomechanical characteristics and immune functions of DCs. When co-cultured with K562 cells, the biomechanical and immunological characteristics of immature DCs (imDCs) and mature DCs (mDCs) were severely impaired compared with controls. The changes include increased membrane viscoelasticity, reorganized cytoskeleton (F-actin), suppressed capability of antigen uptake, transendothelium migration, and activation of naïve T cells. In exploring the mechanisms of these changes, we identified several genes and proteins by microarray analysis and 2D gel electrophoresis. Changes were found in the cytoskeleton-related genes and proteins (such as cofilin1 and profilin1) and matrix-related genes and proteins (such as TIMP1 and MMP9). These findings provide a molecular basis for the biomechanical and immunological changes of DCs in response to K562 and may help to elucidate the mechanism for tumor immune escape.

摘要

树突状细胞 (DCs) 是一种具有强大抗原呈递能力的细胞,被用于传递启动免疫反应所必需的信号。在本研究中,我们采用了一种跨学科的方法来研究 K562 细胞(一种人慢性髓性白血病 (CML) 细胞系)对树突状细胞的生物力学特性和免疫功能的影响。与对照组相比,与 K562 细胞共培养时,未成熟树突状细胞 (imDCs) 和成熟树突状细胞 (mDCs) 的生物力学和免疫学特性受到严重损害。这些变化包括细胞膜粘弹性增加、细胞骨架 (F-actin) 重排、抗原摄取能力、跨内皮迁移能力和幼稚 T 细胞激活能力下降。在探索这些变化的机制时,我们通过微阵列分析和 2D 凝胶电泳鉴定了几个基因和蛋白质。在细胞骨架相关基因和蛋白质(如丝切蛋白 1 和 Profilin1)和基质相关基因和蛋白质(如 TIMP1 和 MMP9)中发现了变化。这些发现为 DCs 对 K562 反应的生物力学和免疫学变化提供了分子基础,并可能有助于阐明肿瘤免疫逃逸的机制。

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Biophysics involved in the process of tumor immune escape.肿瘤免疫逃逸过程中涉及的生物物理学。
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