Summary
Intracellular Ca2+ concentrations ([Ca2+]i) were measured in single-cultured human epithelial intestinal HT-29-D4 cells by digital microscopy using the Ca2+-sensitive fluorescent dye Fura-2. Exposure of these cells to HIV-1 surface-envelope glycoprotein gp120, or to a soluble form of its precursor (gp160), resulted in a significant, dose-dependent rise in [Ca2+]i. gp120 or gp160 specifically abrogated the [Ca2+]i response to the neuropeptide agonist neurotensin, which is a stimulator of chloride secretion via inositol trisphosphate-mediated Ca2+ mobilization. By contrast, upon exposure to neurotensin gp120 failed to show any increase in [Ca2+]i within the same cells, suggesting that both neurotensin and gp120 stimulate a common pathway of [Ca2+]i mobilization. gp120-/gp160-induced [Ca2+]i responses were abolished by preincubation with neutralizing antibodies directed against the third variable domain of gp120. These antibodies inhibited the binding of gp120/gp160 to galactosylceramide (GalCer), the alternative HIV-1 receptor in HT-29-D4 cells. Furthermore, HT-29-D4 cells displayed an important increase in [Ca2+]i to anti-GalCer mAb alone, which rendered the cells insensitive to gp120. By contrast, HT-29-D4 cells became insensitive to anti-GalCer mAb after exposure to gp120. These data indicate that HIV-1 may directly alter enterocytic functions through interaction with the GalCer receptor.
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Kotler, D.P., Gaetze, H.P., Klein, E.B., Lange, M. and Holt, P.R., Ann. Intern. Med., 101 (1984) 421.
Ullrich, R., Zeitz, M., Heise, W., L'Age, M., Hoffken, G. and Riecken, E.O., Ann. Intern. Med., 111 (1989) 15.
Nelson, J.A., Wiley, C.A., Reynolds-Kohler, C., Reese, C.E., Margaretten, W. and Levy, J.A., Lancet i, (1988) 259.
Mathijs, J.M., Hing, M., Grierson, J., Dwyer, D.E., Goldschmidt, C., Cooper, D.A. and Cunningham, A.L., Lancet i, (1988) 1111.
Levy, J.A., Margaretten, W. and Nelson, J., Am. J. Gastroenterol., 84 (1989) 787.
Heise, C., Dandekar, S., Kumar, P., Duplantier, R., Donovan, R.M. and Halsted, C.H., Gastroenterology, 100 (1991) 1521.
Kotler, D.P., Reka, S., Borcich, A. and Cronin, W.J., Am. J. Pathol., 139 (1991) 823.
Bigornia, E., Simon, D., Weiss, L.M., Jones, J., Tanowitz, H., Wittner, M. and Lyman, W., Am. J. Gastroenterol., 87 (1992) 1624.
Ullrich, R., Heise, W., Bergs, C., L'Age, M., Riecken, E.O. and Zeitz, M., Gastroenterology, 102 (1992) 1483.
Mathewson, J.J., Jiang, Z.D., DuPont, H.L., Chintu, C., Luo, N. and Zumla, A., J. Infect. Dis., 169 (1994) 614.
Adachi, A., Koenig, S., Gendelman, H.E., Daugherty, D., Gattoni-Celli, S., Fauci, A. and Martin, M., J. Virol., 61 (1987) 209.
Omary, M.B., Brenner, D.A., de Grandpre, L.Y., Roebuck, K.A., Richman, D.D. and Kagnoff, M.F., Aids, 5 (1991) 275.
Barnett, S.W., Barboza, A., Wilcox, C.M., Fosmark, C.E. and Levy, J.A., Virology, 182 (1991) 902.
Moyer, M.P. and Gendelman, H.E., J. Leukocyte Biol., 49 (1991) 499.
Phillips, D.M. and Bourinbaiar, A.S., Virology, 186 (1992) 261.
Fantini, J., Yahi, N., Baghdiguian, S. and Chermann, J.C., J. Virol., 66 (1992) 580.
Asmuth, D.M., Hammer, S.M., and Wanke, C.A., Aids, 8 (1994) 205.
Yahi, N., Baghdiguian, S., Moreau, H. and Fantini, J., J. Virol., 66 (1992) 4848.
Fantini, J., Cook, D.G., Nathanson, N., Spitalnik, S.L. and Gonzalez-Scarano, F., Proc. Natl. Acad. Sci. USA, 90 (1993) 2700.
Harouse, J.M., Bhat, S., Spitalnik, S.L., Laughlin, M., Stefano, K., Silberberg, D.H. and Gonzalez-Scarano, F., Science, 253 (1991) 320.
Bhat, S., Spitalnik, S.L., Gonzalez-Scarano, F. and Silberberg, D.H., Proc. Natl. Acad. Sci. USA, 88 (1991) 7131.
Long, D., Berson, J.F., Cook, D.G. and Doms, R.W., J. Virol., 68 (1994) 5890.
Bjork, S., Breimer, M.E., Hannson, G.C., Karlsson, K.A. and Leffler, H., J. Biol. Chem., 262 (1987) 6758.
Holgerson, J., Jovall, P.A. and Breimer, M.E., J. Biochem., 110 (1991) 120.
Yahi, N., Spitalnik, S.L., Stefano, K.A., De Micco, P., Gonzalez-Scarano, F. and Fantini, J., Virology, 204 (1994) 550.
Turner, J.T., James-Kracke, M.R. and Camden, J.M., J. Pharmacol. Exp. Ther., 253 (1990) 1049.
Morris, A.P., Kirk, K.L. and Frizzell, R.A., Cell Regul., 1 (1990) 951.
Fantini, J., Yahi, N. and Chermann, J.C., Proc. Natl. Acad. Sci. USA, 88 (1991) 9297.
Dayanithi, G., Yahi, N., Baghdiguian, S. and Fantini, J., Cell Calcium, 18 (1995) 9.
Lambert, R.C., Dayanithi, G., Moos, F.C. and Richard, P., J. Physiol., 478 (1994) 275.
Grynkiewicz, G., Poenie, M. and Tsien, R.Y., J. Biol. Chem., 260 (1985) 3440.
Kieny, M.P., Lathe, R., Rivière, Y., Dott, K., Schmitt, D., Girard, M., Montagnier, L. and Lecoq, J.P., Protein Eng., 2 (1988) 219.
Dreyer, E.B., Kaiser, P.K., Offermann, J.T. and Lipton, S.A., Science, 248 (1990) 364.
Yahi, N., Sabatier, J.M., Nickel, P., Mabrouk, K., Gonzalez-Scarano, F. and Fantini, J., J. Biol. Chem., 269 (1994) 24349.
Cook, D.G., Fantini, J., Spitalnik, S.L. and Gonzalez-Scarano, F., Virology, 201 (1994) 206.
Dyer, C.A. and Benjamins, J.A., J. Cell Biol., 111 (1990) 625.
Dyer, C.A. and Benjamins, J.A., J. Neurosci. Res., 30 (1991) 699.
Lo, T., Falert, C.J., Piser, T.M. and Thayer, S.A., Brain Res., 594 (1992) 189.
Bozou, J.C., Rochet, N., Magnaldo, I., Vincent, J.P. and Kitabgi, P., Biochem. J., 264 (1989) 871.
Berridge, M.J., Nature, 361 (1993) 315.
Donowitz, M. and Welsh, M.J., Annu. Rev. Physiol., 48 (1986) 135.
Morris, A.P., Cunningham, S.A., Benos, D.J. and Frizzel, R.A., J. Biol. Chem., 267 (1992) 5575.
Dobbins, W.O. and Weinstein, W.M., Gastroenterology, 88 (1985) 738.
Benhamou, Y., Hilmarsdottir, I., Desportes-Livage, I., Hoang, C., Datry, A., Danis, M., Gentilini, M. and Opolon, P., Dig. Dis. Sci., 39 (1994) 2163.
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Dayanithi, G., Yahi, N., Baghdiguian, S. et al. Galactosylceramide and transmembrane signalling in enterocytes: Calcium response induced by HIV-1 surface-envelope glycoprotein gp120. Perspectives in Drug Discovery and Design 5, 181–191 (1996). https://doi.org/10.1007/BF02174013
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DOI: https://doi.org/10.1007/BF02174013