Nikolai G, Niggemann B, Werner M, Zänker K S
Institute of Immunology, University of Witten/Herdecke, Witten, Germany.
Immunobiology. 1999 Sep;201(1):107-19. doi: 10.1016/S0171-2985(99)80050-3.
T cell migration within tissue requires engagement of the cytoskeleton, however, little is known about the functional role of both actin- and tubulin-based cytoskeleton in this process. We investigated the direct effect of microtubule disruption and stabilization using colcemid and taxol, respectively, on the locomotion of peripheral human T cells within three-dimensional (3-D) collagen lattices. Microtubules network disassembly very potently enhanced T cell migration, nearly doubling the fraction of locomoting cells. Both a recruitment of previously sessile cells as well as an increase in the mean duration of active locomotion contributed to the promigratory effect. The stimulatory effect was correlated with the loss of the integrity of the tubulin cytoskeleton. Reassembly of microtubules, subsequent to the removal of colcemid from the cells, resulted in the successive return of the migratory activity to baseline levels. On the contrary, taxol failed to modulate T cell migration in our in vitro assay despite its potency to assemble tubulin into compact clots. Our observations underscore the view that tubulin-dependent cellular deformability is not the rate-limiting factor for locomotion and provide evidence that the increase in migratory activity subsequent to colcemid-treatment is due to a secondary phenomenon, most likely the activation of the actin cytoskeleton.
T细胞在组织内的迁移需要细胞骨架的参与，然而，关于基于肌动蛋白和微管蛋白的细胞骨架在此过程中的功能作用，人们所知甚少。我们分别使用秋水仙酰胺和紫杉醇研究了微管破坏和稳定对人外周血T细胞在三维（3-D）胶原晶格中运动的直接影响。微管网络的解体非常有效地增强了T细胞的迁移，使运动细胞的比例几乎增加了一倍。先前静止细胞的募集以及主动运动平均持续时间的增加都有助于产生促迁移作用。这种刺激作用与微管蛋白细胞骨架完整性的丧失相关。从细胞中去除秋水仙酰胺后微管的重新组装导致迁移活性相继恢复到基线水平。相反，尽管紫杉醇能够将微管蛋白组装成紧密的凝块，但在我们的体外试验中它未能调节T细胞迁移。我们的观察结果强调了这样一种观点，即微管蛋白依赖性细胞变形性不是运动的限速因素，并提供了证据表明秋水仙酰胺处理后迁移活性的增加是由于一种继发现象，很可能是肌动蛋白细胞骨架的激活。
