Fibronectin interaction with α4β1 integrin prevents apoptosis in B cell chronic lymphocytic leukemia:: correlation with Bcl-2 and Bax
Fibronectin interaction with α4β1 integrin prevents apoptosis in B cell chronic lymphocytic leukemia:: correlation with Bcl-2 and Bax
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DOI：
10.1038/sj.leu.2401275
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发表时间：
1999-02-01
期刊：
影响因子：
11.4
通讯作者：
Garcia-Pardo, A
中科院分区：
文献类型：
--
作者：
de la Fuente, MT;Casanova, B;Garcia-Pardo, A
B细胞慢性淋巴细胞白血病（B-CLL）由明显逃避正常凋亡调节的恶性细胞的积累组成。我们已经研究了α 4 β 1整合素/纤连蛋白相互作用在体外防止这些细胞凋亡的作用。16例患者的B细胞显示α 4 β 1恒定表达，α 5 β 1表达很少或没有表达。在纤连蛋白或两种先前描述的含有α 4 β 1配体的纤连蛋白重组片段（H89和H 0）上培养的B-CLL细胞始终显示出比在聚赖氨酸上培养的对照细胞更高的存活力。含有高亲和力配体CS-1的H89片段是最有效的底物，在培养第2、5和8天的平均细胞活力值分别为72、60和35%。对于对照细胞，这些值分别为40、27和15%。平行细胞周期分析证实了这些结果。抗凋亡作用需要与固定化基质直接接触，因为当单独使用B-CLL条件培养基或当α 4 β 1与特异性mAb在悬浮液中聚集时未观察到。凋亡调节蛋白Bcl-2和Fax的定量显示，在H89片段上培养的细胞显示出高/中等水平的Bcl-2（具有一些患者间差异）和低水平的Fax，导致Bcl-2/Bax比率升高。这些结果表明B-CLL细胞与纤连蛋白的粘附上调Bcl-2/Bax比率，这可能有助于通过α 4 β 1整联蛋白诱导的抗凋亡作用。
B cell chronic lymphocytic leukemia (B-CLL) consists of the accumulation of malignant cells that apparently escape normal apoptotic regulation. We have studied the role of alpha 4 beta 1 integrin/fibronectin interaction in preventing apoptosis of these cells in vitro. B cells from 16 patients showed constant expression of alpha 4 beta 1 and little or no alpha 5 beta 1. B-CLL cells cultured on fibronectin or two previously described fibronectin recombinant fragments (H89 and H0) which contain the ligands for alpha 4 beta l, consistently showed higher viability than control cells cultured on poly-lysine. The H89 fragment, containing the high affinity ligand CS-1, was the most efficient substrate with mean cell viability values of 72, 60 and 35% at days 2, 5 and 8 of culture, respectively. For control cells these values were 40, 27 and 15%, respectively. Parallel cell cycle analysis confirmed these results. The anti-apoptotic effect required direct contact with immobilized substrata since it was not observed when using B-CLL conditioned media alone or when clustering alpha 4 beta 1 with specific mAbs in suspension. Quantitation of the apoptosis regulatory proteins Bcl-2 and Fax revealed that cells cultured on the H89 fragment showed high/moderate levels of Bcl-2 (with some interpatient variation) and low levels of Fax resulting in an elevated Bcl-2/Bax ratio. These results indicate that adhesion of B-CLL cells to fibronectin upregulate the Bcl-2/Bax ratio and this may contribute to the anti-apoptotic effect induced via alpha 4 beta 1 integrin.