Inositol trisphosphate is generated by a rat natural killer cell tumor in response to target cells or to crosslinked monoclonal antibody OX-34: possible signaling role for the OX-34 determinant during activation by target cells.
RNK-16 cells, rat leukemia cells with features of natural killer (NK) cells, were adapted for growth in vitro and used to examine the mechanism of NK-cell activation. Contact of RNK-16 cells with tumor cells (YAC-1) that are lysed by NK cells, but not with resistant tumor cells (EL-4, K562), led to an increase in inositol trisphosphate (InsP3), a Ca2+-mobilizing messenger. A similar increase in InsP3 could be elicited in RNK-16 cells by monoclonal antibody OX-34, when the antibody was crosslinked by F(ab')2 fragments of goat antibodies to mouse immunoglobulin. This reaction was accompanied by an increase in the concentration of cytoplasmic free calcium Ca2+, due primarily to the release of Ca2+ from intracellular stores. In contrast to the stimulatory effects of crosslinked OX-34, OX-34 alone did not affect the levels of either InsP3 or cytoplasmic free Ca2+. Moreover, OX-34 alone blocked the generation of InsP3 by RNK-16 cells in response to YAC-1 cells and prevented target-cell killing. These findings demonstrate that OX-34 identifies a structure on the surface of RNK-16 cells that can stimulate the generation of InsP3, and they suggest that this structure can regulate signal transduction during target-cell recognition by NK cells.
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm / Q000032:analysis*; D002460:Cell Line; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000378:metabolism*; D007700:Kinetics; D007942:Leukemia, Experimental / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D013403:Sugar Phosphates / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000951:Antigens, Neoplasm; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate