Abstract
VERY little is known about the receptors and target molecules involved in natural killer (NK) cell activity. Here we present a model system in which interleukin-2-activated killing by NK cells depends on the intercellular adhesion molecule ICAM-2 and is regulated by the distribution of ICAM-2. The level of ICAM-2 expression in NK-sensitive and resistant cells is similar, but in sensitive cells ICAM-2 is concentrated into bud-like cellular projections known as uropods, whereas in resistant cells it is evenly distributed. The cytoskeletal–membrane linker protein ezrin is also localized in uropods. Transfection of human ezrin into NK-resistant cells induces uropod formation, redistribution of ICAM-2 and ezrin, and sensitizes target cells to interleukin-2-activated killing. These results reveal a new mechanism of target-cell recognition: cytotoxic cells recognize adhesion molecules that are already present on normal cells, but in diseased cells are concentrated into a biologically active cell-surface region by cytoskeletal reorganization. The results also highlight the importance of cytoskeletal interactions in the regulation of ICAM-2-mediated adhesive phenomena.
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References
Helander, T., Timonen, T., Kalliomäki, P. & Schröder, J. J. Immun. 147, 2063–2067 (1991).
Arpin, M., Algrain, M. & Louvard, D. Curr. Opin. Cell Biol. 6, 136–141 (1994).
Turunen, O. et al. J. biol. Chem. 264, 16727–16732 (1989).
Algrain, M., Turunen, O., Vaheri, A., Louvard, D. & Arpin, M. J. Cell Biol. 120, 129–139 (1993).
Kärre, K. Science 267, 978–979 (1995).
Chambers, W. H. & Brissette-Storkus, C. S. Chem. Biol. 2, 429–435 (1995).
Trinchieri, G. J. exp. Med. 180, 417–421 (1994).
Malnati, M. S. et al. Science 267, 1016–1018 (1995).
Colonna, M. & Samaridis, J. Science 268, 405–408 (1995).
Gumperz, J. E. & Parham, P. Nature 378, 245–248 (1995).
Giorda, R. et al. Science 249, 1298–1300 (1990).
Yokoyama, W. M. & Seaman, W. E. A. Rev. Immun. 11, 613–635 (1993).
Frey, J. L. et al. J. exp. Med. 174, 1527–1536 (1991).
Giardina, S. L. et al. J. Immun. 154, 80–87 (1995).
Garni-Wagner, B. A., Purohit, A., Mathew, P. A., Bennet, M. & Kumar, V. J. Immun. 151, 60–70 (1993).
Valiante, N. M. & Trinchieri, G. J. exp. Med. 178, 1397–1406 (1993).
Dougherty, G. J., Murdoch, S. & Hogg, N. Eur. J. Immun. 18, 35–39 (1988).
Dustin, M. L., Carpén, O. & Springer, T. A. J. Immun. 148, 2654–2663 (1992).
Campanero, M. R. et al. J. Cell Biol. 123, 1007–1016 (1993).
Bretscher, A. J. Cell Biol. 108, 921–930 (1989).
Turunen, O., Wahlström, T. & Vaheri, A. J. Cell Biol. 126, 1445–1453 (1994).
Tsukita, S. et al. J. Cell Biol. 126, 391–401 (1994).
Takeuchi, K. et al. J. Cell Biol. 125, 1371–1384 (1994).
Hanzel, D., Reggio, H., Bretscher, A., Forte, J. G. & Mangeat, P. EMBO J. 10, 2363–2373 (1991).
Gary, R. & Bretscher, A. Proc. natn. Acad. Sci. U.S.A. 90, 10846–10850 (1993).
Andréoli, C., Martin, M., Le Borgne, R., Reggio, H. & Mangeat, P. J. Cell Sci. 107, 2509–2521 (1994).
Martin, M. et al. J. Cell Biol. 128, 1081–1093 (1995).
Pakkanen, R., Bonsdorff, C.-H., Turunen, O., Wahlström, T. & Vaheri, A. Eur. J. Cell Biol. 46, 435–443 (1988).
Julius, M. H., Simpson, E. & Herzenberg, L. A. Eur. J. Immun. 3, 645–649 (1973).
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Helander, T., Carpén, O., Turunen, O. et al. ICAM-2 redistributed by ezrin as a target for killer cells. Nature 382, 265–268 (1996). https://doi.org/10.1038/382265a0
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DOI: https://doi.org/10.1038/382265a0
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