Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Dec;86(24):10039–10043. doi: 10.1073/pnas.86.24.10039

Development of human mast cells in vitro.

T Furitsu 1, H Saito 1, A M Dvorak 1, L B Schwartz 1, A M Irani 1, J F Burdick 1, K Ishizaka 1, T Ishizaka 1
PMCID: PMC298639  PMID: 2532357

Abstract

Nucleated cells of human umbilical cord blood were cocultured with mouse skin-derived 3T3 fibroblasts. After 7-8 weeks in culture, when the number of the other hematopoietic cells declined, metachromatic granule-containing mononuclear cells appeared in the cultures, and the number of the cells increased up to 12 weeks. After 11-14 weeks in culture, the metachromatic mononuclear cells comprised a substantial portion of the cultured cells. These cells contained 1.8-2 micrograms of histamine per 10(6) cells and bore receptors for IgE. All of the cells contained tryptase in their granules. Electron microscopic analysis showed that these cells were mature human mast cells, clearly different from the basophilic granulocytes or eosinophils that arise in a variety of circumstances in cord blood cell cultures. Most of the cultured mast cells expressed some granules with regular crystalline arrays and contained both tryptase and chymase, and thus resembled human skin mast cells.

Full text

PDF
10039

Images in this article

Selected References

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

  1. Castells M. C., Irani A. M., Schwartz L. B. Evaluation of human peripheral blood leukocytes for mast cell tryptase. J Immunol. 1987 Apr 1;138(7):2184–2189. [PubMed] [Google Scholar]
  2. Dayton E. T., Pharr P., Ogawa M., Serafin W. E., Austen K. F., Levi-Schaffer F., Stevens R. L. 3T3 fibroblasts induce cloned interleukin 3-dependent mouse mast cells to resemble connective tissue mast cells in granular constituency. Proc Natl Acad Sci U S A. 1988 Jan;85(2):569–572. doi: 10.1073/pnas.85.2.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dvorak A. M., Hammel I., Schulman E. S., Peters S. P., MacGlashan D. W., Jr, Schleimer R. P., Newball H. H., Pyne K., Dvorak H. F., Lichtenstein L. M. Differences in the behavior of cytoplasmic granules and lipid bodies during human lung mast cell degranulation. J Cell Biol. 1984 Nov;99(5):1678–1687. doi: 10.1083/jcb.99.5.1678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dvorak A. M. Human mast cells. Adv Anat Embryol Cell Biol. 1989;114:1–107. [PubMed] [Google Scholar]
  5. Dvorak A. M., Saito H., Estrella P., Kissell S., Arai N., Ishizaka T. Ultrastructure of eosinophils and basophils stimulated to develop in human cord blood mononuclear cell cultures containing recombinant human interleukin-5 or interleukin-3. Lab Invest. 1989 Jul;61(1):116–132. [PubMed] [Google Scholar]
  6. Horton M. A., O'Brien H. A. Characterization of human mast cells in long-term culture. Blood. 1983 Dec;62(6):1251–1260. [PubMed] [Google Scholar]
  7. Irani A. A., Schechter N. M., Craig S. S., DeBlois G., Schwartz L. B. Two types of human mast cells that have distinct neutral protease compositions. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4464–4468. doi: 10.1073/pnas.83.12.4464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Irani A. M., Bradford T. R., Kepley C. L., Schechter N. M., Schwartz L. B. Detection of MCT and MCTC types of human mast cells by immunohistochemistry using new monoclonal anti-tryptase and anti-chymase antibodies. J Histochem Cytochem. 1989 Oct;37(10):1509–1515. doi: 10.1177/37.10.2674273. [DOI] [PubMed] [Google Scholar]
  9. Ishizaka T., Conrad D. H., Huff T. F., Metcalfe D. D., Stevens R. L., Lewis R. A. Unique features of human basophilic granulocytes developed in in vitro culture. Int Arch Allergy Appl Immunol. 1985;77(1-2):137–143. doi: 10.1159/000233768. [DOI] [PubMed] [Google Scholar]
  10. Kirshenbaum A. S., Goff J. P., Dreskin S. C., Irani A. M., Schwartz L. B., Metcalfe D. D. IL-3-dependent growth of basophil-like cells and mastlike cells from human bone marrow. J Immunol. 1989 Apr 1;142(7):2424–2429. [PubMed] [Google Scholar]
  11. Levi-Schaffer F., Austen K. F., Caulfield J. P., Hein A., Bloes W. F., Stevens R. L. Fibroblasts maintain the phenotype and viability of the rat heparin-containing mast cell in vitro. J Immunol. 1985 Nov;135(5):3454–3462. [PubMed] [Google Scholar]
  12. Levi-Schaffer F., Austen K. F., Caulfield J. P., Hein A., Gravallese P. M., Stevens R. L. Co-culture of human lung-derived mast cells with mouse 3T3 fibroblasts: morphology and IgE-mediated release of histamine, prostaglandin D2, and leukotrienes. J Immunol. 1987 Jul 15;139(2):494–500. [PubMed] [Google Scholar]
  13. Levi-Schaffer F., Austen K. F., Gravallese P. M., Stevens R. L. Coculture of interleukin 3-dependent mouse mast cells with fibroblasts results in a phenotypic change of the mast cells. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6485–6488. doi: 10.1073/pnas.83.17.6485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ogawa M., Nakahata T., Leary A. G., Sterk A. R., Ishizaka K., Ishizaka T. Suspension culture of human mast cells/basophils from umbilical cord blood mononuclear cells. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4494–4498. doi: 10.1073/pnas.80.14.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Razin E., Rifkind A. B., Cordon-Cardo C., Good R. A. Selective growth of a population of human basophil cells in vitro. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5793–5796. doi: 10.1073/pnas.78.9.5793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Razin E., Stevens R. L., Akiyama F., Schmid K., Austen K. F. Culture from mouse bone marrow of a subclass of mast cells possessing a distinct chondroitin sulfate proteoglycan with glycosaminoglycans rich in N-acetylgalactosamine-4,6-disulfate. J Biol Chem. 1982 Jun 25;257(12):7229–7236. [PubMed] [Google Scholar]
  17. Rennick D. M., Lee F. D., Yokota T., Arai K. I., Cantor H., Nabel G. J. A cloned MCGF cDNA encodes a multilineage hematopoietic growth factor: multiple activities of interleukin 3. J Immunol. 1985 Feb;134(2):910–914. [PubMed] [Google Scholar]
  18. Rennick D., Yang G., Muller-Sieburg C., Smith C., Arai N., Takabe Y., Gemmell L. Interleukin 4 (B-cell stimulatory factor 1) can enhance or antagonize the factor-dependent growth of hemopoietic progenitor cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6889–6893. doi: 10.1073/pnas.84.19.6889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Saito H., Hatake K., Dvorak A. M., Leiferman K. M., Donnenberg A. D., Arai N., Ishizaka K., Ishizaka T. Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2288–2292. doi: 10.1073/pnas.85.7.2288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Saito H., Okajima F., Molski T. F., Sha'afi R. I., Ui M., Ishizaka T. Effects of ADP-ribosylation of GTP-binding protein by pertussis toxin on immunoglobulin E-dependent and -independent histamine release from mast cells and basophils. J Immunol. 1987 Jun 1;138(11):3927–3934. [PubMed] [Google Scholar]
  21. Schulman E. S., MacGlashan D. W., Jr, Peters S. P., Schleimer R. P., Newball H. H., Lichtenstein L. M. Human lung mast cells: purification and characterization. J Immunol. 1982 Dec;129(6):2662–2667. [PubMed] [Google Scholar]
  22. Seldin D. C., Caulfield J. P., Hein A., Osathanondh R., Nabel G., Schlossman S. F., Stevens R. L., Austen K. F. Biochemical and phenotypic characterization of human basophilic cells derived from dispersed fetal liver with murine T cell factors. J Immunol. 1986 Mar 15;136(6):2222–2230. [PubMed] [Google Scholar]
  23. Siraganian R. P. An automated continuous-flow system for the extraction and fluorometric analysis of histamine. Anal Biochem. 1974 Feb;57(2):383–394. doi: 10.1016/0003-2697(74)90093-1. [DOI] [PubMed] [Google Scholar]
  24. Tadokoro K., Stadler B. M., De Weck A. L. Factor-dependent in vitro growth of human normal bone marrow-derived basophil-like cells. J Exp Med. 1983 Sep 1;158(3):857–871. doi: 10.1084/jem.158.3.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Valent P., Ashman L. K., Hinterberger W., Eckersberger F., Majdic O., Lechner K., Bettelheim P. Mast cell typing: demonstration of a distinct hematopoietic cell type and evidence for immunophenotypic relationship to mononuclear phagocytes. Blood. 1989 May 15;73(7):1778–1785. [PubMed] [Google Scholar]
  26. Yuen E., Brown R. D., van der Lubbe L., Rickard K. A., Kronenberg H. Identification and characterization of human hemopoietic mast cell colonies. Exp Hematol. 1988 Dec;16(11):896–902. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES