Chappey O N, Niel E, Debray M, Wautier J L, Scherrmann J M
Institut National de la Santé et de la Recherche Médicale U26, Hôpital Fernand Widal, Paris, France.
J Pharmacol Exp Ther. 1995 Sep;274(3):1072-6.
Uptake of [3H]colchicine (2.5 ng/ml) by human lymphocytes in culture was slow in the length of time to reach steady state (> 48 hr) and was limited in the maximal intracellular colchicine amount (1-2% of total extracellular colchicine). Efflux of intracellular colchicine was investigated 40 hr after colchicine cell exposure by using either washing of the extracellular medium or adding different colchicine-specific Fab fragments:colchicine dose molar ratios of 0.5, 1 and 5. Except for the 0.5 dose molar ratio, the kinetics of [3H]colchicine efflux from lymphocytes induced by extracellular specific Fab fragments were similar to those obtained by washing and were characterized by a first-order decline with half-lives ranging from 15.5 to 16.4 hr. These half-lives were in the same range as those characterizing the dissociation of colchicine from the intracellular tubulin receptor. Our data demonstrate that a tightly bound intracellular toxin may be extracted by antibody with high affinity for the toxin present in the extracellular space at a rate depending on the rate of dissociation of the toxin from its receptor.
培养的人淋巴细胞对[3H]秋水仙碱（2.5纳克/毫升）的摄取在达到稳态的时间长度上较慢（>48小时），并且细胞内秋水仙碱的最大量有限（占细胞外秋水仙碱总量的1-2%）。在秋水仙碱与细胞接触40小时后，通过洗涤细胞外培养基或添加不同的秋水仙碱特异性Fab片段：秋水仙碱剂量摩尔比为0.5、1和5，研究了细胞内秋水仙碱的流出情况。除了0.5剂量摩尔比外，细胞外特异性Fab片段诱导的淋巴细胞中[3H]秋水仙碱流出动力学与通过洗涤获得的动力学相似，其特征是一级下降，半衰期为15.5至16.4小时。这些半衰期与秋水仙碱从细胞内微管蛋白受体解离的半衰期在同一范围内。我们的数据表明，一种紧密结合的细胞内毒素可以被对细胞外空间中存在的毒素具有高亲和力的抗体提取，提取速率取决于毒素从其受体解离的速率。
