Signal transduction via phosphorylated adhesion molecule, LFA-1{beta} (CD18), is increased by culture of natural killer cells with IL-2 in the generation of lymphokine-activated killer cells |
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Authors: | Umehara, Hisanori Takashima, Akihiko Minami, Yasuhiro Bloom, Eda T. |
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Affiliation: | 1 Division of Cytokine Biology, Center for Biologies Evaluation and Research FDA, 8800 Rockville Pike, Bethesda, MD 20892, USA 2 Division of Bacterial Products, Center for Biologies Evaluation and Research FDA, 8800 Rockville Pike, Bethesda, MD 20892, USA 3 Cell Biology and Metabolism Branch NICHD, NIH, Bethesda, MD 20892, USA 4Present address: Osaka Dental University 1–5–17 Ootemae, Chuo–ku, Osaka 540, Japan 5Present address: Mitsubishi Kasei Institute of Life Science 11 Minami Ooya, Machida–shi, Japan 6Present address: Institute for Molecular and Cellular Biology, Osaka University 1-3 Yamadaoka, Suita-shi, Osaka 565, Japan |
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Abstract: | It is well known that IL-2 stimulates natural killer (NK) cellsto express lymphokine activated killer (LAK) activity and thatthis stimulation prompts the acquisition of the ability to lysepreviously insensitive target cells. The possible role of adhesionmolecules in the IL-2 activation process was probed by focussingon a lymphocyte function-associated antigen (LFA)-1-dependentmodel system. A mAb to the LFA-1ß chain abrogatedLAK activity, but only moderately suppressed NK activity, suggestinga differential role for LFA-1ß In LAK compared withNK mediated lysis. Orthophosphate labeling demonstrated thatthe LFA-1ß chain was strongly phosphorylated in LAKbut not NK cells; in contrast, the chain was phosphorylatedsimilarlyin both effector cell types. At least a portion ofthe phosphorylation of the ß chain was on tyrosineresidues, as shown by Western blotting with anti-phosphotyrosineantibody of LFA-1ß immunoprecipitates. Crosslinkingof the LFA-1ß chain with plastic-adhered antibodystimulated Ca2+-dependent release of cytoplasmic lytic granulesand induced phosphatidyl inositol turnover in LAK but not NKcells. We conclude that the IL-2-induced phosphorylation oftheß chain of the LFA-1 adhesion molecule in LAK cellsand associated alteration in signal transduction may be importantin the stimulation of LAK cell activity in NK cells. |
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Keywords: | adhesion molecule cytotoxicity human integrin lymphokine activated killer cells natural killer cells phosphorylation |
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