Greene W C, Parker C M, Parker C W
J Immunol. 1976 Sep;117(3):1015-22.
The possible modulatory role of microtubules or closely related colchicine-sensitive structures in the response of human lymphocytes to mitogenic lectins was investigated. Colchicine (0.1 to 10 muM) AND VINBLASTINE (0.1 TO 10 MUM) inhibited early [14C]-aminoisobutyric acid and late [3H]-thymidine uptake in phytohemagglutinin-and concanavalin A-stimulated human lymphocytes but failed to alter 45Ca uptake. Lumicolchicine, an inactive congener of colchicine, was ineffective in all three systems. Both microtubular agents accentuated and prolonged the early cyclic AMP response to lectin. Little or no alteration in cyclic AMP levels was seen with colchicine or vinblastine alone or in combination with PGE (10MUM) or epinephrine (1muM) suggesting that the effect on cyclic AMP metabolism is largely selective for lectin stimulation. Neither microtunular agent altered 125I-concanacalin A binding. Since the inhibition of DNA synthesis was throughout the culture period and early aminoisobutyric acid uptake is affected, it appears that these agents are acting on an early event, or events, in the activation sequence. Although the mechanism of the inhibition is not known, the effect of colchicine and vinblastine in prolonging the cyclic AMP response to lectin may be involved. Alternatively, alterations in microtubules assembly may exert effects on membrane architecture interfering with propagation of the stimulus from the membrane to the cell interior.
研究了微管或与之密切相关的秋水仙碱敏感结构在人淋巴细胞对促有丝分裂凝集素反应中的可能调节作用。秋水仙碱（0.1至10μM）和长春碱（0.1至10μM）抑制了植物血凝素和刀豆球蛋白A刺激的人淋巴细胞早期[14C] - 氨基异丁酸摄取和晚期[3H] - 胸腺嘧啶核苷摄取，但未能改变45Ca摄取。光秋水仙碱是秋水仙碱的无活性类似物，在所有三个系统中均无效。两种微管药物均增强并延长了对凝集素的早期环磷酸腺苷反应。单独使用秋水仙碱或长春碱，或与前列腺素E（10μM）或肾上腺素（1μM）联合使用时，环磷酸腺苷水平几乎没有变化，这表明对环磷酸腺苷代谢的影响在很大程度上是凝集素刺激所特有的。两种微管药物均未改变125I - 刀豆球蛋白A的结合。由于整个培养期间DNA合成均受到抑制，且早期氨基异丁酸摄取也受到影响，因此这些药物似乎作用于激活序列中的早期事件。虽然抑制机制尚不清楚，但秋水仙碱和长春碱在延长凝集素诱导的环磷酸腺苷反应方面的作用可能与之有关。或者，微管组装的改变可能对膜结构产生影响，干扰刺激从膜向细胞内部的传递。
