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KMID : 0391319940040020259
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Korean Journal of Biological Response Modifiers
1994 Volume.4 No. 2 p.259 ~ p.268
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Regulation of Lymphokine-Activated Killer(LAK) Cell Mediated Cytotoxicity in non-Adherent Human PBL
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Abstract
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Background:
@EN Lypmhokines activate a killer cell population of PBL. These LAK (lymphokine activated killer) cells are able to lyse fresh tumor cells as well as cells from in vitro tumor cell lines in a non-MHC-restricted and non-antigen-specific manner.
Little is
known about the mechanism of LAK generation and regulation. We investigated the correlation of LAK cell activity with and IL-2 receptor(Tac) or adhesion molecules. Also the regulation of LAK generation through PKA, PKC and tyrosine kinase pathway
was
examined.
@ES Methods:
@EN Cytotoxicity was measured by analysing fluorescence of live and dead target cells using FACScan. Tyrosine phosphorylation in NK cells was measured by crosslinking NK cells with anti FcγRIII antibody and immunoblotting the cell lysates with
anti
phosphotyrosine antibody using ECLTM(Amersham) western blotting protocol.
@ES Results:
@EN 1) IL-2 significantly induced a killer cell activity as compared to other cytokines and this IL-2 induced cytotoxicity was substantially inhibited by IL-4.
2) The regulation of IL-2 receptor(Tac) expression was well correlated with LAK generation and the IL-2 induced cytotoxicity was efficiently blocked by an antibody to IL-2 receptor.
3) LFA-1(CD11a) expression of effector cells was increased by IL-2, which was also correlated with cytotoxicity and the pretreatment of anti ICAM-1 (CD54) antibody to target cells reduced the IL-2 induced cytotoxicity.
4) dBt-cAMP inhibited the IL-2 induced cytotoxicity in the lytic phase, whereas staurosporin in differentiation phase and genistein in both phases.
5) The induction of LAK cytotoxicity was well correlated with the induction of IL-2 receptor and with FcγRIII expression, the latter of which may participate NK cell signal transduction through activation of tyrosine kinases.
@ES Concusion:
@EN Taken together, the regulation of LAK-meadiated cytotoxicity appears to involve a complex mechanism through IL-2 receptor and adhesion molecules. PKC and tyrosine kinase may play some roles in the differentiation into LAK effector cells,
whereas PKA
and tyrosine kinase mediated pathway may be operative in the lytic process.
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KEYWORD
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