THE CYTO-TOXIC ACTIVITY OF HUMAN NATURAL-KILLER CELLS REQUIRES AN INTACT SECRETORY APPARATUS

THE CYTO-TOXIC ACTIVITY OF HUMAN NATURAL-KILLER CELLS REQUIRES AN INTACT SECRETORY APPARATUS
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DOI:
10.1016/0008-8749(81)90152-0
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发表时间:
1981-01-01
影响因子:
4.3
通讯作者:
SAKSELA, E
SAKSELA, E
中科院分区:
医学4区
文献类型:
--
作者:
CARPEN, O;VIRTANEN, I;SAKSELA, E

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研究了不同细胞分泌和运动抑制物对人自然杀伤细胞(NK细胞)杀伤活性的影响。用高纯度的外周血淋巴细胞作为效应细胞,其中大颗粒淋巴细胞(LGL)占人体NK活性的75-85%。用羧基离子载体莫能菌素处理效应细胞,不可逆地抑制了NK细胞介导的杀伤。该药物阻断高尔基体小泡的囊泡运输,因此该结果有力地表明,人类NK细胞的杀伤活性需要分泌过程。在莫能菌素处理的效应细胞中,孵育24小时内高尔基体区大量糖蛋白积聚。溶解活性不需要完整的微管,因为在长春花碱诱导的含有微管蛋白的准晶体中的效应细胞仍然介导正常的NK活性。人类NK细胞介导的细胞溶解需要能量。在杀伤细胞活性的致死阶段之前,效应器和靶细胞之间形成了密切的接触,需要活跃的细胞运动和二价阳离子[镁和钙]。
The effect of various inhibitors of cellular secretion and motility on the cytolytic activity of human natural killer (NK) cells was studied. As effector cells, highly purified peripheral blood lymphocytes consisting of 75-85% large granular lymphocytes (LGL) that were responsible for the NK activity in man were used. Treatment of the effector cells with a carboxylic ionophore monensin irreversibly inhibited the NK-cell-mediated killing. This drug interrupts the vesicular traffic of Golgi-derived vesicles and thus the results strongly suggested that secretory processes are required in human NK cell cytolytic activity. In the monensin-treated effector cells large glycoprotein amounts accumulated in the Golgi area within 24 h of incubation. The lytic activity did not require intact microtubules since effector cells in which vinblastine-induced tubulin-containing paracrystals were demonstrated still mediated normal NK activity. Energy was required in the human NK-cell-mediated cytolysis. The lethal hit stage of the cytolytic activity was preceded by formation of intimate contacts between effector and target cells and required active cell movement and divalent cations [Mg2+ and Ca2+].