Co-ligation of α 4 β 1 integrin and TCR rescues human thymocytes from steroid-induced apoptosis
Co-ligation of α 4 β 1 integrin and TCR rescues human thymocytes from steroid-induced apoptosis
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α 4 β 1 整合素和 TCR 的共连接可挽救人类胸腺细胞免受类固醇诱导的细胞凋亡
DOI：
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
H. Golding
中科院分区：
文献类型：
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作者：
M. Zaitseva;C. Mojcik;D. Salomon;E. Shevach;H. Golding
胸腺细胞的成熟代表一系列事件，在此期间，表达对自身抗原/MHC具有中等亲合力的TCR的胸腺细胞被阳性选择，而具有高或不足TCR亲合力的胸腺细胞死亡。糖皮质激素在胸腺内产生，并可促进胸腺细胞凋亡。胸腺细胞在与表达血管粘附分子-1（VCAM-1）并分泌糖皮质激素的上皮细胞、与骨髓来源的巨噬细胞以及与含有纤连蛋白（FN）和胶原的细胞外基质的密切接触中分化。它们与FN的接触由α4β1和α5β1整合素介导。我们研究了TCR和整合素信号转导对地塞米松（Dex）诱导的胸腺细胞凋亡的存活的贡献。我们证明FN和VCAM-1（两者都结合α4β1整联蛋白），而不是胶原蛋白，显著增强TCR介导的胸腺细胞对Dex诱导的凋亡的保护。这种“存活”信号通过α4β1转导，但不通过α5β1整联蛋白。所观察到的Dex诱导的细胞凋亡的保护与bcl-2蛋白水平的增加相关。FN- α4β1和VCAM-1- α4β1结合可诱导bcl-2蛋白表达上调，而α5β1与FN结合可诱导负性信号，抗α5β1抗体可阻断该信号。这些数据表明，α4β1整合素可能有助于保护具有中等亲和力TCR的胸腺细胞免受胸腺内成熟过程中糖皮质激素诱导的死亡。
Maturation of thymocytes represents a sequence of events during which thymocytes expressing TCR with moderate avidity for self antigen/MHC are positively selected, whereas those with high or insufficient TCR avidity die. Glucocorticoids are produced intrathymically and can contribute to apoptosis of unselected thymocytes. Thymocytes differentiate in a close contact with epithelial cells, expressing vascular adhesion molecule-1 (VCAM-1) and secreting glucocorticoids, with bone marrow-derived macrophages, and with extracellular matrix containing fibronectin (FN) and collagen. Their contact with FN is mediated by α4β1 and α5β1 integrins. We examined the contribution of TCR and integrin signaling to the survival of thymocytes from dexamethasone (Dex)-induced apoptosis. We demonstrate that FN and VCAM-1 (both of which bind α4β1 integrin), but not collagen, considerably augment TCR-mediated protection of thymocytes from Dex-induced apoptosis. This ‘survival’ signal is transduced through the α4β1, but not through the α5β1 integrin. The observed protection from Dex-induced apoptosis correlated with an increase in bcl-2 protein levels. FN– α4β1 and VCAM-1– α4β1 engagement induced up-regulation bcl-2 protein, while α5β1 binding to FN induced a negative signal that was blocked by antiα5β1 antibody. These data suggest that α4β1 integrin may contribute to protection of thymocytes with moderate avidity TCR from glucocorticoid-induced death during intrathymic maturation.
DOI：
10.1073/pnas.92.11.4763
发表时间：
1995-05-23
影响因子：
11.1
作者：
MA, A;PENA, JC;THOMPSON, CB
通讯作者：
THOMPSON, CB
影响因子：
3.3
作者：
MEREDITH, JE;FAZELI, B;SCHWARTZ, MA
通讯作者：
SCHWARTZ, MA