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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Jan;91(1):148–152. doi: 10.1172/JCI116164

Reversible expansion of primate mast cell populations in vivo by stem cell factor.

S J Galli 1, A Iemura 1, D S Garlick 1, C Gamba-Vitalo 1, K M Zsebo 1, R G Andrews 1
PMCID: PMC330008  PMID: 7678600

Abstract

Mast cell development in mice is critically regulated by stem cell factor (SCF), the term used here to designate a product of fibroblasts and other cell types that is a ligand for the tyrosine kinase receptor protein encoded by the proto-oncogene c-kit. However, the factors which regulate the size of mast cell populations in primates are poorly understood. Here we report that the subcutaneous administration of recombinant human SCF (rhSCF) to baboons (Papio cynocephalus) or cynomolgus monkeys (Macaca fascicularis) produced a striking expansion of mast cell populations in many anatomical sites, with numbers of mast cells in some organs of rhSCF-treated monkeys exceeding the corresponding values in control monkeys by more than 100-fold. Animals treated with rhSCF did not exhibit clinical evidence of mast cell activation, and discontinuation of treatment with rhSCF resulted in a rapid decline of mast cell numbers nearly to baseline levels. These findings are the first to demonstrate that a specific cytokine can regulate mast cell development in primates in vivo. They also provide the first evidence, in any mammalian species, to indicate that the cytokine-dependent expansion of tissue mast cell populations can be reversed when administration of the cytokine is discontinued.

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Selected References

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  1. Andrews R. G., Knitter G. H., Bartelmez S. H., Langley K. E., Farrar D., Hendren R. W., Appelbaum F. R., Bernstein I. D., Zsebo K. M. Recombinant human stem cell factor, a c-kit ligand, stimulates hematopoiesis in primates. Blood. 1991 Oct 15;78(8):1975–1980. [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. 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]
  4. 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]
  5. 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]
  6. Furitsu T., Saito H., Dvorak A. M., Schwartz L. B., Irani A. M., Burdick J. F., Ishizaka K., Ishizaka T. Development of human mast cells in vitro. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10039–10043. doi: 10.1073/pnas.86.24.10039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Galli S. J. New insights into "the riddle of the mast cells": microenvironmental regulation of mast cell development and phenotypic heterogeneity. Lab Invest. 1990 Jan;62(1):5–33. [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Kitamura Y., Yokoyama M., Matsuda H., Ohno T., Mori K. J. Spleen colony-forming cell as common precursor for tissue mast cells and granulocytes. Nature. 1981 May 14;291(5811):159–160. doi: 10.1038/291159a0. [DOI] [PubMed] [Google Scholar]
  11. Martin F. H., Suggs S. V., Langley K. E., Lu H. S., Ting J., Okino K. H., Morris C. F., McNiece I. K., Jacobsen F. W., Mendiaz E. A. Primary structure and functional expression of rat and human stem cell factor DNAs. Cell. 1990 Oct 5;63(1):203–211. doi: 10.1016/0092-8674(90)90301-t. [DOI] [PubMed] [Google Scholar]
  12. Metcalfe D. D. The liver, spleen, and lymph nodes in mastocytosis. J Invest Dermatol. 1991 Mar;96(3):45S–46S. [PubMed] [Google Scholar]
  13. Rottapel R., Reedijk M., Williams D. E., Lyman S. D., Anderson D. M., Pawson T., Bernstein A. The Steel/W transduction pathway: kit autophosphorylation and its association with a unique subset of cytoplasmic signaling proteins is induced by the Steel factor. Mol Cell Biol. 1991 Jun;11(6):3043–3051. doi: 10.1128/mcb.11.6.3043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Travis W. D., Li C. Y., Bergstralh E. J., Yam L. T., Swee R. G. Systemic mast cell disease. Analysis of 58 cases and literature review. Medicine (Baltimore) 1988 Nov;67(6):345–368. [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. 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]
  20. Wingren U., Enerbäck L. Mucosal mast cells of the rat intestine: a re-evaluation of fixation and staining properties, with special reference to protein blocking and solubility of the granular glycosaminoglycan. Histochem J. 1983 Jun;15(6):571–582. doi: 10.1007/BF01954148. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]

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