SIGNAL TRANSDUCTION IN ACTIVATED NATURAL-KILLER-CELLS AND NATURAL-KILLER-CELLS INACTIVATED WITH SENSITIVE TARGETS

被引:0
|
作者
GIBBONEY, JJ [1 ]
SHENOY, AM [1 ]
JIN, X [1 ]
BRAHMI, Z [1 ]
机构
[1] INDIANA UNIV,SCH MED,DEPT MED,702 BARNHILL DR,RI 509,INDIANAPOLIS,IN 46202
关键词
NATURAL KILLER CELLS; PROTEIN KINASE-C; PHOSPHATIDYLINOSITOL; ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY;
D O I
暂无
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We have recently demonstrated that the activation of NK cells involves a protein-kinase-C (PKC)-dependent step as well as a phosphatidylinositol (PI)-linked signal transduction system. We have also shown that when NK cells are incubated with sensitive targets for up to 6 h they lose their lytic potential and require IL-2 to regain their lytic activity. PKC is involved in many cell processes such as the transduction of hormonal signals and the machinery of cellular secretion and is activated by diacylglycerol and by a number of phorbol esters, including phorbol myristic acid (PMA). To reinforce the role of PKC in NK-cell-mediated cytotoxicity, we first showed that NK-CMC is inhibited by two agents that inhibit PKC activation, staurosporine and sphingosine. Next, we showed that antibody-dependent cellular cytotoxicity of NK-resistant targets was PKC dependent and Ca2+ dependent. Further, we showed that PMA plus ionophore alone could induce NK killing of resistant targets and that this killing was PKC and Ca2+ dependent. Finally, we contrasted the role of PKC in these activated cells to the role of PKC in cells that have been inactivated with a sensitive target, K562. We showed that PKC is not required for the IL-2-dependent reactivation of NK cells but that Ca2+ is required. To further determine what event in signal transduction is inactivated by K562, we showed that inactivated NK cells do not turnover PI in response to K562 stimulation.
引用
收藏
页码:57 / 68
页数:12
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