Macrophage spreading in vitro. III. The effect of metabolic inhibitors, anesthetics and other drugs on spreading induced by subtilisin.
Macrophage spreading in vitro. III. The effect of metabolic inhibitors, anesthetics and other drugs on spreading induced by subtilisin.
复制标题
巨噬细胞在体外扩散。
DOI：
10.1016/0014-4827(74)90629-6
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发表时间：
1974
影响因子：
3.7
通讯作者：
M. Destefano
中科院分区：
文献类型：
--
作者：
Michel Rabinovitch;M. Destefano
定量检测了某些药物对蛋白水解酶枯草杆菌素诱导的巨噬细胞扩散的影响，并测定了药物的 50% 和 90% 抑制浓度。在大多数情况下，巨噬细胞的活力得以保留，如吞噬细胞测试和实验所示，在这些实验中，用药物预处理并洗涤的细胞在暴露于枯草杆菌蛋白酶时显示出扩散。电子传递抑制剂、氧化磷酸化抑制剂或解偶联剂在相当小的浓度下均能有效阻止巨噬细胞的扩散，表明需要 ATP。中性或阳离子麻醉剂也会抑制扩散，并且其 50% 抑制浓度的倒数与其辛醇-水分配系数呈线性相关。麻醉剂的抑制作用与它们对其他膜现象的影响相平行，例如神经传导、红细胞渗透裂解、病毒诱导的细胞融合或肉瘤 I 细胞与基质的粘附，也表明存在膜靶点。抗炎药吲哚美辛或保泰松、高剂量的秋水仙碱或长春花碱、推定的微丝作用药物细胞松弛素 B 或 SH-试剂乙基马来酰亚胺可减少扩散。秋水仙碱和长春花碱的作用可能涉及微管作用以外的机制。其他几种药物，包括蛋白质合成抑制剂，并不能抑制巨噬细胞的扩散。由底物结合的免疫复合物诱导的扩散也被代表性的代谢抑制剂或麻醉剂抑制。
The effect of certain drugs on macrophage spreading induced by the proteolytic enzyme sub-tilisin was quantitatively examined and the 50 and 90 % inhibitory concentrations of the drugs were determined. In most instances the viability of the macrophages was preserved, as shown by phagocytic tests and by experiments in which cells pretreated with the drugs and washed were shown to spread when exposed to subtilisin. Inhibitors of electron transport, oxidative phosphorylation or uncouplers at rather small concentrations all effectively blocked macrophage spreading, indicating an ATP requirement. Spreading was also inhibited by neutral or cationic anesthetics and the reciprocal of their 50 % inhibitory concentrations was linearly related to their octanol-water partition coefficients. Inhibition by the anesthetics paralleled their effects on other membrane phenomena, such as nerve conduction, osmotic lysis of erythrocytes, viral induced cell fusion, or Sarcoma I cell to substrate adhesion, also suggesting a membrane target. Spreading was reduced by the anti-inflammatories indomethacin, or phenylbutazone, by high doses of colchicine or vinblastine, by the putative microfilament-acting drug cytochalasin B or by the SH- reagentn-ethyl maleimide. Colchicine and vinblastine effects may involve mechanisms other than their microtubular actions. Several other drugs, including inhibitors of protein synthesis, did not inhibit the spreading of macrophages. Spreading induced by substrate-bound immune complexes was also inhibited by representative metabolic inhibitors or anesthetics.