Soluble VCAM-1 binding to α4 integrins is cell-type specific and activation dependent and is disrupted during apoptosis in T cells
Soluble VCAM-1 binding to α4 integrins is cell-type specific and activation dependent and is disrupted during apoptosis in T cells
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DOI：
10.1182/blood.v95.2.602
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发表时间：
2000-01-15
期刊：
影响因子：
20.3
通讯作者：
Ginsberg, MH
中科院分区：
文献类型：
--
作者：
Rose, DM;Cardarelli, PM;Ginsberg, MH
可溶性血管细胞粘附分子-1（sVCAM-1）在炎症过程中产生，并可改变淋巴细胞功能。作者报道sVCAM-1与α 4整合素携带细胞的结合是一个动态调节的活性细胞过程。重组sVCAM-1与外周血单个核细胞α 4整合素的结合具有细胞类型特异性。循环中的CD 16 + NK细胞以高亲和力组成性结合sVCAM-1，而T淋巴细胞亚群，主要是CD 45 RO+（记忆），仅在佛波醇酯刺激后结合sVCAM-1。sVCAM-1与同源稳定细胞系的结合也是细胞类型特异性的，并且需要活跃的细胞过程，因为它被ATP合成的抑制和Fas诱导的细胞凋亡阻断。事实上，高亲和力VCAM-1结合的丧失是细胞凋亡的早期事件。此外，H-Ras/Raf-initiated信号通路也抑制sVCAM-1与α 4 β 1整合素的结合。总的来说，这些结果表明α 4整联蛋白结合VCAM-1的能力受到主动调节，并且这种调节可以控制α 4整联蛋白依赖性细胞功能。
Soluble vascular cell adhesion molecule-1 (sVCAM-1) is generated during inflammation and can alter lymphocyte functions. The authors report that the binding of sVCAM-1 to alpha 4 integrin-bearing cells is a dynamically regulated, active cellular process. Binding of recombinant sVCAM-1 to alpha 4 integrins on peripheral blood mononuclear cells was cell-type specific. Circulating CD16+ NK cells constitutively bound sVCAM-1 with high affinity, whereas a subpopulation of T-lymphocytes, primarily CD45RO+ (memory), bound sVCAM-1 only after phorbol ester stimulation. sVCAM-1 binding to homogenous stable cell lines was also cell-type specific, and required active cellular processes because it was blocked by the inhibition of ATP synthesis and by Fas-induced apoptosis, Indeed, the loss of high-affinity VCAM-1 binding was an early event in apoptosis. Furthermore, an H-Ras/Raf-initiated signaling pathway also suppressed sVCAM-1 binding to alpha 4 beta 1 integrins. Collectively, these results showed that the capacity of alpha 4 integrins to bind VCAM-1 is actively regulated and that this regulation may control alpha 4 integrin-dependent cellular functions.