EFFECTS OF TAXOL AND TAXOL HYPERTHERMIA TREATMENTS ON THE FUNCTIONAL POLARIZATION OF CYTOTOXIC LYMPHOCYTES-T

EFFECTS OF TAXOL AND TAXOL HYPERTHERMIA TREATMENTS ON THE FUNCTIONAL POLARIZATION OF CYTOTOXIC LYMPHOCYTES-T
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DOI:
10.1002/cm.970240206
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发表时间:
1993-01-01
影响因子:
--
通讯作者:
BROWN, DL
BROWN, DL
中科院分区:
其他
文献类型:
--
作者:
KNOX, JD;MITCHEL, REJ;BROWN, DL

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免疫荧光染色,电子显微镜,和(Cr-51)细胞溶解释放试验被用来研究紫杉醇和紫杉醇/热疗治疗的微管组织和细胞毒性T淋巴细胞(CTL)的细胞溶解活性的影响。用1 μ M紫杉醇处理CTL 4小时,导致微管系统广泛重组,形成从中心体延伸的一到几个大的微管束。高尔基体不会被这种处理破坏,并且仍然与微管组织中心(MTOC)相关联。这种微管重组对CTL将其MTOC定向于结合的靶细胞的能力没有影响,也对它们的细胞溶解活性没有影响。在未用紫杉醇处理的对照CTL中,轻度高温处理(42 ℃,30 min)导致中心粒周围物质的聚集、MTOC取向的丧失、细胞溶解活性的抑制和微管系统的解体[Knox et al.:Exp. Cell Res. 194:275-283,1991]。相比之下,在紫杉醇处理的CTL中,稳定的微管束不受这种热疗处理的影响;然而,热疗的其他作用在对照和紫杉醇处理的CTL中似乎相同。这些结果表明,一个动态的,径向排列的微管阵列是不需要的CTL的功能极化,并建议的pericentriolar材料的一个组成部分可能发挥关键作用,影响MTOC的方向。
Immunofluorescence staining, electron microscopy, and (Cr-51) cytolytic release assays are used to investigate the effects of taxol and taxol/hyperthermia treatments on the microtubule organization and cytolytic activity of cytotoxic T lymphocytes (CTLs). A 4 h treatment of CTLs with 1 muM taxol results in an extensive reorganization of the microtubule system to form one to a few large microtubule bundles that extend from the centrosome. The Golgi apparatus is not disrupted by this treatment and remains associated with the microtubule organizing centre (MTOC). This microtubule reorganization has no effect on the ability of CTLs to orient their MTOC towards a bound target cell, nor on their cytolytic activity. In control CTLs, not treated with taxol, a mild hyperthermia treatment (42-degrees-C, 30 min) results in an aggregation of the pericentriolar material, a loss of MTOC orientation, an inhibition of cytolytic activity, and a disorganization of the microtubule system [Knox et al.: Exp. Cell Res. 194:275-283, 1991]. In contrast, in taxol-treated CTLs the stabilized microtubule bundles are unaffected by such hyperthermia treatment; however, the other effects of hyperthermia appear identical in control and taxol-treated CTLs. These results indicate that a dynamic, radially arranged microtubule array is not required for the functional polarization of CTLs and suggest that a component of the pericentriolar material may play a key role in effecting MTOC orientation.