Abstract
THE IgE-triggered release of mast cell mediators in response to antigen is thought to be the primary event in immediate hypersensi-tivity reactions such as systemic anaphylaxis1. Although mast cells and basophils can be activated in vitro by non-IgE stimuli2–5, it is not known whether these triggers lead to physiological changes in vivo. To investigate this possibility, we generated mice with a homozygous null mutation of the Cε gene. Such mice make no IgE, but produce other immunoglobulin isotypes normally. We report that despite the IgE deficiency, sensitized mutant mice become anaphylactic on antigen challenge and display tachycardia and pulmonary function changes similar to those seen in wild-type animals. These responses are accompanied by vascular leak, sharply elevated plasma histamine and rapid death. IgE-indepen-dent anaphylaxis does not depend on complement activation, but, as indicated in studies using genetically immunodeficient RAG-2-SCID mice, does require a functional immune system. Such results clearly demonstrate that non-IgE pathways for hypersensi-tivity reactions exist in mice.
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References
Stevens, R. L. & Austen, K. F. Immun. Today 10, 381–386 (1989).
Fox, P. C., Basciano, L. K. & Siraganian, R. P. J. Immun. 129, 314–319 (1982).
Katz, H. R. et al. J. Immun. 148, 868–871 (1992).
Daeron, M., Couderc, J., Ventura, M., Liacopoulos, P. & Voisin, G. A. Cell. Immun. 70, 27–40 (1982).
Hook, W. A., Siraganian, R. P. & Wahl, S. M. J. Immun. 114, 1185–1190 (1975).
Shimizu, A., Takahashi, N., Yaoita, Y. & Honjo, T. Cell 28, 499–506 (1982).
Shimuzu, A. et al. Nature 289, 149–153 (1981).
Rothman, P., Li, S. C. & Alt, F. Semin. Immun. 1, 65–77 (1989).
Mu, H.-H. & Sewell, W. A. Infect. Immun. 61, 2834–2840 (1993).
Munoz, J. J., Peacock, M. G. & Hadlow, W. J. Infect. Immun. 55, 1004–1008 (1987).
Munoz, J. J. & Peacock, M. G. Cell. Immun. 127, 327–336 (1990).
Clausen, C. R., Munoz, J. & Bergman, R. K. J. Immun. 104, 312–319 (1970).
Martin, T. R., Galli, S. J., Katona, I. M. & Drazen, J. M. J. clin. Invest. 83, 1375–1383 (1989).
Martin, T. R. et al. J. Immun. 151, 367–376 (1993).
Van den Berg, C. W., Aerts, P. C. & Van Kijk, H. J. immun. Meth. 136, 287–294 (1991).
Saloga, J. et al. J. clin. Invest. 91, 133–140 (1993).
Vaz, E. M., Silveira, I. H. S., Dodd, V. M. B., Monteiro, M. R. & Vaz, N. M. Int. Arch. Allergy 39, 459–468 (1970).
Nussenzweig, R. S., Merryman, C. & Benacerraf, B. J. exp. Med. 120, 315–328 (1964).
Bosma, G. C., Custer, R. P. & Bosma, M. J. Nature 301, 527–530 (1983).
Shinkai, Y. et al. Cell 68, 855–867 (1992).
Arimura, A. et al. Immunol. Invest. 19, 227–233 (1990).
Inagaki, N., Miura, T., Nagai, H. & Koda, A. Jap. J. Pharm. 59, 201–208 (1992).
Dombrowicz, D., Flamand, V., Brigman, K. K., Koller, B. H. & Kinet, J.-P. Cell 75, 979–976 (1993).
Silvers, W. S. Ann. Allergy 68, 58–63 (1992).
Sun, S. et al. J. Lab. clin. Med. 120, 589–596 (1992).
Takai, T., Li, M., Sylvestre, D., Clynes, R. & Ravetch, J. V. Cell 76, 519–529 (1994).
Tybulewicz, V. L., Crawford, C. E., Jackson, P. K., Bronson, R. T. & Mulligan, R. C. Cell 65, 1153–1163 (1991).
Li, E., Bestor, T. H. & Jaenisch, R. Cell 69, 915–926 (1992).
Rothman, P., Lutzker, W., Cook, R., Coffman, R. & Alt, F. J. exp. Med. 168, 2385–2389 (1988).
Klerx, J. P. A. M., Beukelman, C. J., Van Dijk, H. & Willers, J. M. N. J. immun. Meth. 63, 215–220 (1983).
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Oettgen, H., Martin, T., Wynshaw-Boris, A. et al. Active anaphylaxis in IgE-deficient mice. Nature 370, 367–370 (1994). https://doi.org/10.1038/370367a0
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DOI: https://doi.org/10.1038/370367a0
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