BLOCKING OF HUMAN LYMPHOCYTE-T ACTIVATION BY CHANNEL ANTAGONISTS
BLOCKING OF HUMAN LYMPHOCYTE-T ACTIVATION BY CHANNEL ANTAGONISTS
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DOI：
10.1002/cbf.290070311
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发表时间：
1989-07-01
影响因子：
3.6
通讯作者：
ROSEMBLATT, MS
中科院分区：
文献类型：
--
作者：
BONO, MR;SIMON, V;ROSEMBLATT, MS
已经确定，淋巴细胞活化的早期事件涉及细胞内Ca++的升高以及其他离子通量的变化。虽然Ca++通道已被假定参与早期Ca++升高，但其在淋巴细胞中的存在仍然存在争议。此外，虽然尚未检测到，电生理数据表明存在的Ca++激活的K+通道对人外周血淋巴细胞（HPBL）。在这里，我们报告的影响，具体的通道阻滞剂作为一种方法来识别这些通道上HPBL。在40 nM硝苯地平，电压老化的Ca++通道的抑制剂，完全抑制PHA促进的HPBL激活。这种效应是浓度依赖性的，半峰效应约为10 nM，并且无论药物是在加入促分裂原的同时加入还是在加入促分裂原后18 h加入，都是可以证明的。如果使用IL-2而不是PHA激活淋巴细胞，则看不到这种激活抑制。Charybdotoxin是一种阻断肌细胞Ca++激活的K+通道的毒素，它也几乎100%阻断PHA诱导的HPBL激活。无论阻滞剂是否与PHA一起添加或在PHA后4小时内添加，都可以证明这种抑制作用。与硝苯地平相反，如果在活化过程开始后18小时加入，则Charybdotoxin没有显示出效果。当硝苯地平和Charybdotoxin对小鼠脾细胞进行测试时，我们发现硝苯地平完全抑制LPS促进的这些细胞的活化，而Charybdotoxin对其活化没有影响。总之，这些结果加强了关于电压老化的Ca++通道和Ca++激活的K+通道参与人T淋巴细胞活化的观点。
It has been established that early events in lymphocyte activation involve a rise in intracellular Ca++ as well as changes in the flux of other ions. Although a Ca++ channel has been postulated to participate in the early Ca++ rise, its presence in lymphocytes remains controversial. Also although yet undetected, electrophysiological data suggest the presence of a Ca++ activated K+ channel on human peripheral blood lymphocytes (HPBL). Here we report on the effect of specific channel blockers as an approach to the identification of these channels on HPBL. At 40 nM nifedipine, an inhibitor of voltage-aged Ca++ channels, fully inhibits the PHA-promoted activation of HPBL. This effect is concentration dependent with a half maximum effect at approximately 10 nM and is demonstrable whether the drug is added at the same time as or up to 18 h after the addition of the mitogen. This inhibition of activation is not seen if the lymphocytes are activated using IL-2 instead of PHA. Charybdotoxin a toxin which blocks a Ca++ activated K+ channel of muscle cells also blocks to almost 100 per cent the PHA-induced activation of HPBL. This inhibition can be demonstrated regardless of whether the blocker is added together with or up to 4h after PHA. As opposed to nifedipine charybdotoxin shows no effect if added 18h after the initiation of the activation process. When nifedipine and charybdotoxin were tested on mice splenocytes we found that nifedipine fully inhibits the LPS-promoted activation of these cells while charybdotoxin has no effect on their activation. Taken together these results strengthen the view regarding the participation of both a voltage-aged Ca++ channel and a Ca++ activated K+ channel in human T lymphocyte activation.