Rac regulates integrin-mediated spreading and increased adhesion of T lymphocytes
Rac regulates integrin-mediated spreading and increased adhesion of T lymphocytes
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DOI：
10.1128/mcb.18.7.3936
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发表时间：
1998-07-01
影响因子：
5.3
通讯作者：
Van Aelst, L
中科院分区：
文献类型：
--
作者：
D'Souza-Schorey, C;Boettner, B;Van Aelst, L
白细胞粘附到细胞外基质（ECM）受到严格控制，对免疫反应至关重要。循环淋巴细胞离开血液，附着在炎症和淋巴组织部位的ECM成分上。调节t淋巴细胞- ecm粘附的机制包括(i)细胞表面整合素受体对其细胞外配体亲和力的改变和（ii）受体占用后事件的改变（例如，细胞扩散）。虽然H-Ras和R-Ras先前被证明通过改变整合素受体的亲和力状态来影响t细胞的粘附，但尚未发现第二种机制的信号分子。在这项研究中，我们证明了激活的Rac突变体的表达引发了T细胞的急剧扩散，并以整合素依赖的方式增加了固定纤维连接蛋白上的粘附。ARF6的Rho、Cdc42、H-Ras等激活突变体的表达没有模仿这种效应，这表明pac在该事件中的独特作用。rac诱导的扩散伴随着特异性的细胞骨架重排；此外，在细胞粘附部位和扩散细胞的外周边缘也观察到整合素的聚集。我们证明RacV12的表达不会改变细胞表面整合素的表达水平或整合素受体的亲和力状态。此外，我们的研究结果表明，Rac通过涉及细胞扩散的机制在t细胞粘附调节中发挥作用，而不是通过改变整合素受体的表达水平或亲和力。此外，我们发现rac介导的导致T淋巴细胞扩散的信号通路不需要激活c-Jun激酶、血清反应因子或pp70（S6）激酶，但似乎涉及磷脂激酶。
Leukocyte adhesion to the extracellular matrix (ECM) is tightly controlled and is vital for the immune response. Circulating lymphocytes leave the bloodstream and adhere to ECM components at sites of inflammation and lymphoid tissues. Mechanisms for regulating T-lymphocyte-ECM adhesion include (i) an alteration in the affinity of cell surface integrin receptors for their extracellular ligands and (ii) an alteration of events following postreceptor occupancy (e.g., cell spreading). Whereas H-Ras and R-Ras were previously shown to affect T-cell adhesion by altering the affinity state of the integrin receptors, no signaling molecule has been identified for the second mechanism. In this study, we demonstrated that expression of an activated mutant of Rac triggered dramatic spreading of T cells and their increased adhesion on immobilized fibronectin in an integrin-dependent manner. This effect was not mimicked by expression of activated mutant forms of Rho, Cdc42, H-Ras, of ARF6, indicating the unique role of pac in this event. The Rac-induced spreading was accompanied by specific cytoskeletal rearrangements; Also, a clustering of integrins at sites of cell adhesion and at the peripheral edges of spread cells was observed. We demonstrate that expression of RacV12 did not alter the level of expression of cell surface integrins or the affinity state of the integrin receptors. Moreover, our results indicate that Rac plays a role in the regulation of T-cell adhesion by a mechanism involving cell spreading, rather than by altering the level of expression or the affinity of the integrin receptors. Furthermore, we show that the Rac-mediated signaling pathway leading to spreading of T lymphocytes did not require activation of c-Jun kinase, serum response factor, or pp70(S6) (kinase) but appeared to involve a phospholipid kinase.