Research Abstract |
For the improvement of adoptive immune therapy, we investigated the mechanisms of the major side effects, vascular leak syndrome and functional roles of membrane lipid rafts of NK cells. We found 1) After identification of the receptor for fractalkine, CX3CR1, we reported that CX3CR1 was expressed on CD 14+ monocytes, CD 16+ NK cells and CD8+ T cells. 2) Integrins and fractalkine synergistically enhanced cell adhesion. 3) Fractalkine enhanced cell adhesion and granular exocytosis of NK cells. Fractalkine expressed on activated endothelial cells caused NK cell lysis and vascular injury. 4) Fractalkine activated NK cells and produced IFN-gamma, which may mediate Th1-type immune response. 5) Membrane lipid rafts was involved in cytotoxicity of NK cells. 6) Sphingomyelin of the membrane was important for cellular activation and apoptosis. These results may provide the new insight for the improvement for adoptive immune therapy by reducing its side effects, vascular leak syndrome, and improved the efficacy of therapy.
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