Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Oct;92(4):1639–1649. doi: 10.1172/JCI116749

Effects of chronic treatment with the c-kit ligand, stem cell factor, on immunoglobulin E-dependent anaphylaxis in mice. Genetically mast cell-deficient Sl/Sld mice acquire anaphylactic responsiveness, but the congenic normal mice do not exhibit augmented responses.

A Ando 1, T R Martin 1, S J Galli 1
PMCID: PMC288322  PMID: 7691882

Abstract

We treated genetically mast cell-deficient WCB6F1-Sl/Sld mice and the congenic normal (WCB6F1(-)+/+) mice with the c-kit ligand recombinant rat stem cell factor164 (rrSCF164; 100 micrograms/kg per d, subcutaneously) or with vehicle for 21 d, then passively sensitized the mice with anti-dinitrophenol30-40 immunoglobulin E (IgE) antibodies, and 1 d later measured the changes in heart rate, pulmonary dynamic compliance, and pulmonary conductance, and assessed the death rates associated with intravenous challenge of these animals with specific antigen. rrSCF164 treatment induced the development of mast cells in Sl/Sld mice, and these mice exhibited tachycardia, but not death, after challenge with IgE and antigen. rrSCF164 treatment induced mast cell hyperplasia in +/+ mice, but the cardiopulmonary changes associated with passive anaphylaxis in these mice were virtually indistinguishable from those observed in control +/+ mice treated with vehicle instead of rrSCF164. Moreover, the highest dose of antigen challenge produced significantly fewer fatalities in rrSCF164-treated than in vehicle-treated +/+ mice (1/11 vs. 8/11, respectively, P < 0.01). Thus, in normal mice, chronic treatment with rrSCF164 induces mast cell hyperplasia but does not increase, and in certain respects diminishes, the severity of IgE-dependent anaphylactic reactions.

Full text

PDF
1639

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. M., Lyman S. D., Baird A., Wignall J. M., Eisenman J., Rauch C., March C. J., Boswell H. S., Gimpel S. D., Cosman D. Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell. 1990 Oct 5;63(1):235–243. doi: 10.1016/0092-8674(90)90304-w. [DOI] [PubMed] [Google Scholar]
  2. Bischoff S. C., Dahinden C. A. c-kit ligand: a unique potentiator of mediator release by human lung mast cells. J Exp Med. 1992 Jan 1;175(1):237–244. doi: 10.1084/jem.175.1.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coleman J. W., Holliday M. R., Kimber I., Zsebo K. M., Galli S. J. Regulation of mouse peritoneal mast cell secretory function by stem cell factor, IL-3 or IL-4. J Immunol. 1993 Jan 15;150(2):556–562. [PubMed] [Google Scholar]
  4. Columbo M., Horowitz E. M., Botana L. M., MacGlashan D. W., Jr, Bochner B. S., Gillis S., Zsebo K. M., Galli S. J., Lichtenstein L. M. The human recombinant c-kit receptor ligand, rhSCF, induces mediator release from human cutaneous mast cells and enhances IgE-dependent mediator release from both skin mast cells and peripheral blood basophils. J Immunol. 1992 Jul 15;149(2):599–608. [PubMed] [Google Scholar]
  5. Copeland N. G., Gilbert D. J., Cho B. C., Donovan P. J., Jenkins N. A., Cosman D., Anderson D., Lyman S. D., Williams D. E. Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell. 1990 Oct 5;63(1):175–183. doi: 10.1016/0092-8674(90)90298-s. [DOI] [PubMed] [Google Scholar]
  6. Flanagan J. G., Chan D. C., Leder P. Transmembrane form of the kit ligand growth factor is determined by alternative splicing and is missing in the Sld mutant. Cell. 1991 Mar 8;64(5):1025–1035. doi: 10.1016/0092-8674(91)90326-t. [DOI] [PubMed] [Google Scholar]
  7. Flanagan J. G., Leder P. The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. Cell. 1990 Oct 5;63(1):185–194. doi: 10.1016/0092-8674(90)90299-t. [DOI] [PubMed] [Google Scholar]
  8. Galli S. J., Arizono N., Murakami T., Dvorak A. M., Fox J. G. Development of large numbers of mast cells at sites of idiopathic chronic dermatitis in genetically mast cell-deficient WBB6F1-W/Wv mice. Blood. 1987 Jun;69(6):1661–1666. [PubMed] [Google Scholar]
  9. Galli S. J., Iemura A., Garlick D. S., Gamba-Vitalo C., Zsebo K. M., Andrews R. G. Reversible expansion of primate mast cell populations in vivo by stem cell factor. J Clin Invest. 1993 Jan;91(1):148–152. doi: 10.1172/JCI116164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Galli S. J., Tsai M., Wershil B. K. The c-kit receptor, stem cell factor, and mast cells. What each is teaching us about the others. Am J Pathol. 1993 Apr;142(4):965–974. [PMC free article] [PubMed] [Google Scholar]
  11. Gurish M. F., Ghildyal N., McNeil H. P., Austen K. F., Gillis S., Stevens R. L. Differential expression of secretory granule proteases in mouse mast cells exposed to interleukin 3 and c-kit ligand. J Exp Med. 1992 Apr 1;175(4):1003–1012. doi: 10.1084/jem.175.4.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ha T. Y., Reed N. D., Crowle P. K. Immune response potential of mast cell-deficient W/Wv mice. Int Arch Allergy Appl Immunol. 1986;80(1):85–94. doi: 10.1159/000234031. [DOI] [PubMed] [Google Scholar]
  13. Ha T. Y., Reed N. D. Systemic anaphylaxis in mast-cell-deficient mice of W/Wv and Sl/Sld genotypes. Exp Cell Biol. 1987;55(2):63–68. doi: 10.1159/000163399. [DOI] [PubMed] [Google Scholar]
  14. Huang E., Nocka K., Beier D. R., Chu T. Y., Buck J., Lahm H. W., Wellner D., Leder P., Besmer P. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell. 1990 Oct 5;63(1):225–233. doi: 10.1016/0092-8674(90)90303-v. [DOI] [PubMed] [Google Scholar]
  15. Irani A. M., Nilsson G., Miettinen U., Craig S. S., Ashman L. K., Ishizaka T., Zsebo K. M., Schwartz L. B. Recombinant human stem cell factor stimulates differentiation of mast cells from dispersed human fetal liver cells. Blood. 1992 Dec 15;80(12):3009–3021. [PubMed] [Google Scholar]
  16. Jacoby W., Cammarata P. V., Findlay S., Pincus S. H. Anaphylaxis in mast cell-deficient mice. J Invest Dermatol. 1984 Oct;83(4):302–304. doi: 10.1111/1523-1747.ep12340431. [DOI] [PubMed] [Google Scholar]
  17. Kirshenbaum A. S., Goff J. P., Kessler S. W., Mican J. M., Zsebo K. M., Metcalfe D. D. Effect of IL-3 and stem cell factor on the appearance of human basophils and mast cells from CD34+ pluripotent progenitor cells. J Immunol. 1992 Feb 1;148(3):772–777. [PubMed] [Google Scholar]
  18. Kitamura Y., Go S. Decreased production of mast cells in S1/S1d anemic mice. Blood. 1979 Mar;53(3):492–497. [PubMed] [Google Scholar]
  19. Liu F. T., Bohn J. W., Ferry E. L., Yamamoto H., Molinaro C. A., Sherman L. A., Klinman N. R., Katz D. H. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol. 1980 Jun;124(6):2728–2737. [PubMed] [Google Scholar]
  20. Martin T. R., Galli S. J., Katona I. M., Drazen J. M. Role of mast cells in anaphylaxis. Evidence for the importance of mast cells in the cardiopulmonary alterations and death induced by anti-IgE in mice. J Clin Invest. 1989 Apr;83(4):1375–1383. doi: 10.1172/JCI114025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Martin T. R., Gerard N. P., Galli S. J., Drazen J. M. Pulmonary responses to bronchoconstrictor agonists in the mouse. J Appl Physiol (1985) 1988 Jun;64(6):2318–2323. doi: 10.1152/jappl.1988.64.6.2318. [DOI] [PubMed] [Google Scholar]
  22. Mitsui H., Furitsu T., Dvorak A. M., Irani A. M., Schwartz L. B., Inagaki N., Takei M., Ishizaka K., Zsebo K. M., Gillis S. Development of human mast cells from umbilical cord blood cells by recombinant human and murine c-kit ligand. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):735–739. doi: 10.1073/pnas.90.2.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takeishi T., Martin T. R., Katona I. M., Finkelman F. D., Galli S. J. Differences in the expression of the cardiopulmonary alterations associated with anti-immunoglobulin E-induced or active anaphylaxis in mast cell-deficient and normal mice. Mast cells are not required for the cardiopulmonary changes associated with certain fatal anaphylactic responses. J Clin Invest. 1991 Aug;88(2):598–608. doi: 10.1172/JCI115344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tsai M., Shih L. S., Newlands G. F., Takeishi T., Langley K. E., Zsebo K. M., Miller H. R., Geissler E. N., Galli S. J. The rat c-kit ligand, stem cell factor, induces the development of connective tissue-type and mucosal mast cells in vivo. Analysis by anatomical distribution, histochemistry, and protease phenotype. J Exp Med. 1991 Jul 1;174(1):125–131. doi: 10.1084/jem.174.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tsai M., Takeishi T., Thompson H., Langley K. E., Zsebo K. M., Metcalfe D. D., Geissler E. N., Galli S. J. Induction of mast cell proliferation, maturation, and heparin synthesis by the rat c-kit ligand, stem cell factor. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6382–6386. doi: 10.1073/pnas.88.14.6382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Valent P., Spanblöchl E., Sperr W. R., Sillaber C., Zsebo K. M., Agis H., Strobl H., Geissler K., Bettelheim P., Lechner K. Induction of differentiation of human mast cells from bone marrow and peripheral blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long-term culture. Blood. 1992 Nov 1;80(9):2237–2245. [PubMed] [Google Scholar]
  27. Wershil B. K., Murakami T., Galli S. J. Mast cell-dependent amplification of an immunologically nonspecific inflammatory response. Mast cells are required for the full expression of cutaneous acute inflammation induced by phorbol 12-myristate 13-acetate. J Immunol. 1988 Apr 1;140(7):2356–2360. [PubMed] [Google Scholar]
  28. Wershil B. K., Tsai M., Geissler E. N., Zsebo K. M., Galli S. J. The rat c-kit ligand, stem cell factor, induces c-kit receptor-dependent mouse mast cell activation in vivo. Evidence that signaling through the c-kit receptor can induce expression of cellular function. J Exp Med. 1992 Jan 1;175(1):245–255. doi: 10.1084/jem.175.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Williams D. E., Eisenman J., Baird A., Rauch C., Van Ness K., March C. J., Park L. S., Martin U., Mochizuki D. Y., Boswell H. S. Identification of a ligand for the c-kit proto-oncogene. Cell. 1990 Oct 5;63(1):167–174. doi: 10.1016/0092-8674(90)90297-r. [DOI] [PubMed] [Google Scholar]
  30. Williams D. E., de Vries P., Namen A. E., Widmer M. B., Lyman S. D. The Steel factor. Dev Biol. 1992 Jun;151(2):368–376. doi: 10.1016/0012-1606(92)90176-h. [DOI] [PubMed] [Google Scholar]
  31. Zsebo K. M., Williams D. A., Geissler E. N., Broudy V. C., Martin F. H., Atkins H. L., Hsu R. Y., Birkett N. C., Okino K. H., Murdock D. C. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell. 1990 Oct 5;63(1):213–224. doi: 10.1016/0092-8674(90)90302-u. [DOI] [PubMed] [Google Scholar]
  32. Zsebo K. M., Wypych J., McNiece I. K., Lu H. S., Smith K. A., Karkare S. B., Sachdev R. K., Yuschenkoff V. N., Birkett N. C., Williams L. R. Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver--conditioned medium. Cell. 1990 Oct 5;63(1):195–201. doi: 10.1016/0092-8674(90)90300-4. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES