Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences.

Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences.
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DOI:
10.1084/jem.179.4.1307
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发表时间:
1994-04-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Ginsberg MH
Ginsberg MH
中科院分区:
其他
文献类型:
--
作者:
Faull RJ;Kovach NL;Harlan JM;Ginsberg MH

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我们发现,T淋巴样细胞对固定化纤维连接蛋白的黏附可以通过两种不同的机制来增加。第一种是通过使用抗β1整合素单抗8A2增加纤维连接蛋白受体/配体相互作用的亲和力。第二种是用佛波酯(PMA)处理细胞,它改变受体占据后发生的事件(例如,细胞扩散),而不影响受体亲和力。在生理浓度的可溶性纤维连接蛋白存在的情况下,这两种机制对黏附的影响表明它们具有不同的生物学后果。在这些条件下,增加纤维连接蛋白受体亲和力的净效果是减少细胞黏附,而PMA诱导的黏附增加不受影响。这表明,在这些情况下,高亲和力受体主要不能用于细胞黏附,它们有另一种功能。我们进一步表明,单核细胞系THP-1的分化或T淋巴样细胞系HUT-78上的T细胞受体复合体的交联都可以诱导可溶性纤维连接蛋白的高亲和力结合。分化的单核细胞表达两组纤维连接蛋白受体:少数处于高亲和力状态,大多数处于低亲和力状态。因此,它们都将在生理浓度的可溶性纤维连接蛋白存在的情况下继续黏附,并在细胞表面结合大量的可溶性纤维连接蛋白。
We show that the adhesion of T lymphoid cells to immobilized fibronectin can be increased by two distinct mechanisms. The first is by increasing the affinity of the fibronectin receptor/ligand interaction using the anti-beta 1 integrin monoclonal antibody 8A2. The second is by treating the cells with phorbol 12-myristate 13-acetate (PMA), which alters events that occur after receptor occupancy (e.g., cell spreading) without affecting receptor affinity. The effects of these two mechanisms on adhesion in the presence of physiological concentrations of soluble fibronectin suggest that they have different biological consequences. Under these conditions, the net effect of increasing the affinity of the fibronectin receptors is to decrease cell adhesion, whereas the increase in adhesion induced by PMA is unaffected. This suggests that the high affinity receptors are not primarily available for cell adhesion under these circumstances, and that they have an alternative function. We further show that high affinity binding of soluble fibronectin can be induced by either differentiation of the monocytic cell line THP-1 or by cross-linking the T cell receptor complexes on the T lymphoid cell line HUT-78. The differentiated monocytic cells express two populations of fibronectin receptors: a minority in a high affinity state, and the majority in a low affinity state. Thus they will both continue to adhere in the presence of physiological concentrations of soluble fibronectin and bind significant amounts of soluble fibronectin at the cell surface.