• Media type: E-Article
  • Title: 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
  • Contributor: Seaman, William E.; Eriksson, Eréne; Dobrow, Robert; Imboden, John B.
  • Published: National Academy of Sciences of the United States of America, 1987
  • Published in: Proceedings of the National Academy of Sciences of the United States of America, 84 (1987) 12, Seite 4239-4243
  • Language: English
  • ISSN: 0027-8424
  • Origination:
  • Footnote:
  • Description: 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 (InsP<sub>3</sub>), a Ca<sup>2+</sup>-mobilizing messenger. A similar increase in InsP<sub>3</sub> could be elicited in RNK-16 cells by monoclonal antibody OX-34, when the antibody was crosslinked by F(ab<sup>′</sup>)<sub>2</sub> fragments of goat antibodies to mouse immunoglobulin. This reaction was accompanied by an increase in the concentration of cytoplasmic free calcium Ca<sup>2+</sup>, due primarily to the release of Ca<sup>2+</sup> from intracellular stores. In contrast to the stimulatory effects of crosslinked OX-34, OX-34 alone did not affect the levels of either InsP<sub>3</sub> or cytoplasmic free Ca<sup>2+</sup>. Moreover, OX-34 alone blocked the generation of InsP<sub>3</sub> 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 InsP<sub>3</sub>, and they suggest that this structure can regulate signal transduction during target-cell recognition by NK cells.
  • Access State: Open Access