Up-regulation of IL-2 induced lymphokine activated killer cell activity by cisplatin and FK-565: involvement of calcium ion.
As reported earlier, the IL-2 induced lymphokine activated killer (LAK) activity is significantly up-regulated in the presence of cisplatin/FK-565. Based on these observations, we have investigated whether calcium is involved in the generation of LAK activity by IL-2 alone or along with CP/FK-565. We have shown that treatment of PBMC with IL-2 for four days caused an increase in intracellular free calcium and in ATP levels, which were further significantly enhanced when LAK cells were generated in the presence of CP/FK-565. Depletion of calcium resulted in decreased cytotoxic activity. Addition of tumor cells to LAK cells, generated in the presence of IL-2 alone or along with CP/FK-565 caused an instant rise in intracellular free calcium which was significantly decreased when an increase in intracellular free calcium was observed in calcium-free, EGTA-containing buffer. These data suggest that calcium is required for the activation and manifestation of lytic activity by LAK cells. Further, we observed that the increase in intracellular free calcium is not associated with the blastogenic response of peripheral blood mononuclear cells in response to treatment of IL-2 alone or together with CP/FK-565.
Sodhi
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A
School of Biotechnology, Banaras Hindu University, Varanasi, India.
Basu
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S
D000255:Adenosine Triphosphate / Q000032:analysis; D002118:Calcium / Q000032:analysis*; D002945:Cisplatin / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D008213:Lymphocyte Activation; D009842:Oligopeptides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D007376:Interleukin-2; D009842:Oligopeptides; D000255:Adenosine Triphosphate; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine; D002945:Cisplatin; D002118:Calcium