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首页> 外文期刊>Signal transduction: Receptors, mediators and genes: Official journal of the Signal Transduction Society >Activation-dependent FasL expression in T lymphocytes and Natural Killer cells
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Activation-dependent FasL expression in T lymphocytes and Natural Killer cells

机译：T淋巴细胞和自然杀伤细胞中激活依赖的FasL表达

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摘要

In cytotoxic T cells and Natural Killer cells, the death factor FasL is stored in association with secretory granules. Only upon activation, these vesicles are transported to the cytotoxic immunological synapse and FasL is expressed on the cell surface. Upon activation of T cells and NK cells with phorbol ester and calcium ionophore, we observed a biphasic expression of FasL in all lymphocyte subsets tested. The first peak was seen after 10-15 minutes of stimulation and was followed by a reduction of expression to baseline level before the second peak was reached at about two hours. Using inhibitors of protein biosynthesis (cycloheximide), vesicular transport (brefeldin A and monensin), actin polymerization (latrunculin A and cytochalasin D) and metalloproteases (GM 6001 and phenanthrolin), the regulation of FasL expression was analyzed in detail. We demonstrate that the first wave of expression is due to an actin-dependent mobilization of preformed FasL whereas the second phase of expression requires de novo synthesis. The observed expression patterns might have implications for the development of therapeutic strategies that target FasL as an immunomodulatory protein.
机译：在细胞毒性T细胞和自然杀伤细胞中，死亡因子FasL与分泌颗粒一起储存。仅在激活时，这些囊泡才被转运至细胞毒性免疫突触，并且FasL在细胞表面表达。在使用佛波酯和钙离子载体激活T细胞和NK细胞后，我们观察到所有测试的淋巴细胞亚群中FasL呈双相表达。在刺激10-15分钟后看到第一个峰，随后在约两个小时到达第二个峰之前将表达降低至基线水平。使用蛋白质生物合成抑制剂（环己酰亚胺），囊泡转运蛋白（布雷菲德菌素A和莫能菌素），肌动蛋白聚合抑制剂（扁豆素A和细胞松弛素D）和金属蛋白酶（GM 6001和菲咯啉），详细分析了FasL表达的调节。我们证明表达的第一波是由于肌动蛋白依赖性动员的预制FasL，而表达的第二阶段则需要从头合成。观察到的表达模式可能对靶向FasL作为免疫调节蛋白的治疗策略的发展有影响。

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