Dendritic cells from CML patients have altered actin organization, reduced antigen processing, and impaired migration
Dendritic cells from CML patients have altered actin organization, reduced antigen processing, and impaired migration
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DOI：
10.1182/blood-2002-06-1841
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发表时间：
2003-05-01
期刊：
影响因子：
20.3
通讯作者：
Lombardi, G
中科院分区：
文献类型：
--
作者：
Dong, R;Cwynarski, K;Lombardi, G
慢性髓系白血病的特点是表达bcr-abl融合基因，该融合基因编码210 kDa的蛋白，是一种具有结构性活性的酪氨酸激酶。至少70%的癌蛋白定位于细胞骨架，p210(BCR-ABL)最突出的几种酪氨酸激酶底物是细胞骨架蛋白。树突状细胞(DC)是一种骨髓源性抗原提呈细胞，负责启动免疫反应。在民用患者中，高达98%的外周血单个核细胞产生的髓系树突状细胞bcr-abl阳性。在这项研究中，我们比较了来自CML患者和来自健康人的对照DC的髓系树突状细胞的形态和行为。我们发现，髓系来源的CML-DC黏附于FN的肌动蛋白、细胞骨架和形态与正常DC显著不同。CML-DC在处理和呈递外源性抗原(如破伤风类毒素)方面也存在缺陷。与健康人产生的DC相比，抗原处理缺陷可能是CML-DC通过巨噬细胞吞噬或通过甘露糖受体捕获抗原的能力降低的结果。此外，趋化因子诱导的CML-DC在体外的迁移显著减少。这些观察结果不能用民事DC和正常DC成熟状态的差异来解释，因为表型分析。流式细胞仪检测显示成熟标志物的表面表达类似。综上所述，这些结果提示，我们在CML-DC中观察到的抗原处理和迁移的缺陷可能与p210(bcr-abl)融合蛋白诱导的潜在细胞骨架变化有关。(C)2003年，由美国血液病学会提供。
Chronic myeloid leukemia (CIVIL) is characterized by expression of the BCR-ABL fusion gene that encodes a 210-kDa protein, which is a constitutively active tyrosine kinase. At least 70% of the oncoprotein is localized to the cytoskeleton, and several of the most prominent tyrosine kinase substrates for p210(BCR-ABL) are cytoskeletal proteins. Dendritic cells (DCs) are bone marrow-derived antigen-presenting cells responsible for the initiation of immune responses. In CIVIL patients, up to 98% of myeloid DCs generated from peripheral blood mononuclear cells are BCR-ABL positive. In this study we have compared the morphology and behavior of myeloid DCs derived from CML patients with control DCs from healthy individuals. We show that the actin cytoskeleton and shape of CML-DCs of myeloid origin adherent to flbronectin differ significantly from those of normal DCs. CML-DCs are also defective in processing and presentation of exogenous antigens such as tetanous toxoid. The antigen-processing defect may be a consequence of the reduced capacity of CML-DCs to capture antigen via macropinocytosis or via mannose receptors when compared with DCs generated from healthy individuals. Furthermore, chemokine-induced migration of CML-DCs in vitro was significantly reduced. These observations cannot be explained by a difference in the maturation status of CIVIL and normal DCs, because phenotypic analysis. by flow cytometry showed a similar surface expression of maturation makers. Taken together, these results suggest that the defects in antigen processing and migration we have observed in CML-DCs may be related to underlying cytoskeletal changes induced by the p210(BCR-ABL) fusion protein. (C) 2003 by The American Society of Hematology.