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. 1989 Jul 1;170(1):245–257. doi: 10.1084/jem.170.1.245

Interleukin 3-dependent and -independent mast cells stimulated with IgE and antigen express multiple cytokines

PMCID: PMC2189362  PMID: 2473161

Abstract

In response to IgE and specific multivalent antigen, mast cell lines (both growth factor-dependent and -independent) induce the transcription and/or secretion of a number of cytokines having a wide spectrum of activities. We have identified IL-1, IL-3, IL-5, IL-6, IFN- gamma, GM-CSF, JE, MIP1 alpha, MIP1 beta, and TCA3 RNA in at least two of four mast cell clones. The production of these products (except JE) is activation-associated and can be induced by IgE plus antigen. In selected instances cytokine expression can also be induced by activation with Con A or phorbol ester plus ionophore, albeit to levels less than those observed with IgE plus antigen. In addition, long-term mast cell clones and primary cultures of bone marrow-derived mast cells specifically release IL-1, IL-4, and/or IL-6 bioactivity after activation. These findings suggest that in addition to their inflammatory effector function mast cells may serve as a source of growth and regulatory factors. The relationship of mast cells to cells of the T lymphocyte lineage is discussed.

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Selected References

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  1. Abe T., Ochiai H., Minamishima Y., Nawa Y. Induction of intestinal mastocytosis in nude mice by repeated injection of interleukin-3. Int Arch Allergy Appl Immunol. 1988;86(3):356–358. doi: 10.1159/000234597. [DOI] [PubMed] [Google Scholar]
  2. Bach M. K., Brashler J. R. Inhibition of IgE and compound 48/80-induced histamine release by lectins. Immunology. 1975 Aug;29(2):371–386. [PMC free article] [PubMed] [Google Scholar]
  3. Bottomly K. A functional dichotomy in CD4+ T lymphocytes. Immunol Today. 1988 Sep;9(9):268–274. doi: 10.1016/0167-5699(88)91308-4. [DOI] [PubMed] [Google Scholar]
  4. Brown K. D., Zurawski S. M., Mosmann T. R., Zurawski G. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J Immunol. 1989 Jan 15;142(2):679–687. [PubMed] [Google Scholar]
  5. Brown M. A., Pierce J. H., Watson C. J., Falco J., Ihle J. N., Paul W. E. B cell stimulatory factor-1/interleukin-4 mRNA is expressed by normal and transformed mast cells. Cell. 1987 Aug 28;50(5):809–818. doi: 10.1016/0092-8674(87)90339-4. [DOI] [PubMed] [Google Scholar]
  6. Burd P. R., Freeman G. J., Wilson S. D., Berman M., DeKruyff R., Billings P. R., Dorf M. E. Cloning and characterization of a novel T cell activation gene. J Immunol. 1987 Nov 1;139(9):3126–3131. [PubMed] [Google Scholar]
  7. Burd P. R., Rollins B. J., Wilson S. D., Billings P. R., Stiles C. D., Dorf M. E. Comparison of fibroblast and T-cell activation genes. Cell Immunol. 1988 Sep;115(2):481–483. doi: 10.1016/0008-8749(88)90200-6. [DOI] [PubMed] [Google Scholar]
  8. Burnet F. M. The probable relationship of some or all mast cells to the T-cell system. Cell Immunol. 1977 May;30(2):358–360. doi: 10.1016/0008-8749(77)90079-x. [DOI] [PubMed] [Google Scholar]
  9. Campos-Neto A., Stashenko P. P. Interleukin 1 and T-cell activation. Immunol Today. 1988 May;9(5):131–131. doi: 10.1016/0167-5699(88)91196-6. [DOI] [PubMed] [Google Scholar]
  10. Chung S. W., Wong P. M., Shen-Ong G., Ruscetti S., Ishizaka T., Eaves C. J. Production of granulocyte-macrophage colony-stimulating factor by Abelson virus-induced tumorigenic mast cell lines. Blood. 1986 Nov;68(5):1074–1081. [PubMed] [Google Scholar]
  11. Coffman R. L., Carty J. A T cell activity that enhances polyclonal IgE production and its inhibition by interferon-gamma. J Immunol. 1986 Feb 1;136(3):949–954. [PubMed] [Google Scholar]
  12. Coffman R. L., Seymour B. W., Lebman D. A., Hiraki D. D., Christiansen J. A., Shrader B., Cherwinski H. M., Savelkoul H. F., Finkelman F. D., Bond M. W. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev. 1988 Feb;102:5–28. doi: 10.1111/j.1600-065x.1988.tb00739.x. [DOI] [PubMed] [Google Scholar]
  13. Davatelis G., Tekamp-Olson P., Wolpe S. D., Hermsen K., Luedke C., Gallegos C., Coit D., Merryweather J., Cerami A. Cloning and characterization of a cDNA for murine macrophage inflammatory protein (MIP), a novel monokine with inflammatory and chemokinetic properties. J Exp Med. 1988 Jun 1;167(6):1939–1944. doi: 10.1084/jem.167.6.1939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Davatelis G., Wolpe S. D., Sherry B., Dayer J. M., Chicheportiche R., Cerami A. Macrophage inflammatory protein-1: a prostaglandin-independent endogenous pyrogen. Science. 1989 Feb 24;243(4894 Pt 1):1066–1068. doi: 10.1126/science.2646711. [DOI] [PubMed] [Google Scholar]
  15. Dvorak A. M., Galli S. J. Antigen-induced, IgE-mediated degranulation of cloned immature mast cells derived from normal mice. Am J Pathol. 1987 Mar;126(3):535–545. [PMC free article] [PubMed] [Google Scholar]
  16. Freeman G. J., Clayberger C., DeKruyff R., Rosenblum D. S., Cantor H. Sequential expression of new gene programs in inducer T-cell clones. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4094–4098. doi: 10.1073/pnas.80.13.4094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Furutani Y., Nomura H., Notake M., Oyamada Y., Fukui T., Yamada M., Larsen C. G., Oppenheim J. J., Matsushima K. Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). Biochem Biophys Res Commun. 1989 Feb 28;159(1):249–255. doi: 10.1016/0006-291x(89)92430-3. [DOI] [PubMed] [Google Scholar]
  18. Galli S. J., Dvorak A. M., Marcum J. A., Ishizaka T., Nabel G., Der Simonian H., Pyne K., Goldin J. M., Rosenberg R. D., Cantor H. Mast cell clones: a model for the analysis of cellular maturation. J Cell Biol. 1982 Nov;95(2 Pt 1):435–444. doi: 10.1083/jcb.95.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Galli S. J., Dvorak A. M., Marcum J. A., Nabel G., Goldin J. M., Rosenberg R. D., Cantor H., Dvorak H. F. Mouse mast cell clones: modulation of functional maturity in vitro. Monogr Allergy. 1983;18:166–170. [PubMed] [Google Scholar]
  20. Gough N. M., Gough J., Metcalf D., Kelso A., Grail D., Nicola N. A., Burgess A. W., Dunn A. R. Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. 1984 Jun 28-Jul 4Nature. 309(5971):763–767. doi: 10.1038/309763a0. [DOI] [PubMed] [Google Scholar]
  21. Humphries R. K., Abraham S., Krystal G., Lansdorp P., Lemoine F., Eaves C. J. Activation of multiple hemopoietic growth factor genes in Abelson virus-transformed myeloid cells. Exp Hematol. 1988 Oct;16(9):774–781. [PubMed] [Google Scholar]
  22. Ishizaka T., White J. R., Saito H. Activation of basophils and mast cells for mediator release. Int Arch Allergy Appl Immunol. 1987;82(3-4):327–332. doi: 10.1159/000234218. [DOI] [PubMed] [Google Scholar]
  23. Kaye J., Porcelli S., Tite J., Jones B., Janeway C. A., Jr Both a monoclonal antibody and antisera specific for determinants unique to individual cloned helper T cell lines can substitute for antigen and antigen-presenting cells in the activation of T cells. J Exp Med. 1983 Sep 1;158(3):836–856. doi: 10.1084/jem.158.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kurt-Jones E. A., Hamberg S., Ohara J., Paul W. E., Abbas A. K. Heterogeneity of helper/inducer T lymphocytes. I. Lymphokine production and lymphokine responsiveness. J Exp Med. 1987 Dec 1;166(6):1774–1787. doi: 10.1084/jem.166.6.1774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lee F., Yokota T., Otsuka T., Meyerson P., Villaret D., Coffman R., Mosmann T., Rennick D., Roehm N., Smith C. Isolation and characterization of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor 1 activities and T-cell- and mast-cell-stimulating activities. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2061–2065. doi: 10.1073/pnas.83.7.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Lomedico P. T., Gubler U., Hellmann C. P., Dukovich M., Giri J. G., Pan Y. C., Collier K., Semionow R., Chua A. O., Mizel S. B. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. 1984 Nov 29-Dec 5Nature. 312(5993):458–462. doi: 10.1038/312458a0. [DOI] [PubMed] [Google Scholar]
  28. Metcalf D., Begley C. G., Johnson G. R., Nicola N. A., Lopez A. F., Williamson D. J. Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice. Blood. 1986 Jul;68(1):46–57. [PubMed] [Google Scholar]
  29. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  30. Nabel G., Galli S. J., Dvorak A. M., Dvorak H. F., Cantor H. Inducer T lymphocytes synthesize a factor that stimulates proliferation of cloned mast cells. Nature. 1981 May 28;291(5813):332–334. doi: 10.1038/291332a0. [DOI] [PubMed] [Google Scholar]
  31. Nordan R. P., Pumphrey J. G., Rudikoff S. Purification and NH2-terminal sequence of a plasmacytoma growth factor derived from the murine macrophage cell line P388D1. J Immunol. 1987 Aug 1;139(3):813–817. [PubMed] [Google Scholar]
  32. Paul W. E., Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. doi: 10.1146/annurev.iy.05.040187.002241. [DOI] [PubMed] [Google Scholar]
  33. Pierce J. H., Di Fiore P. P., Aaronson S. A., Potter M., Pumphrey J., Scott A., Ihle J. N. Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanism. Cell. 1985 Jul;41(3):685–693. doi: 10.1016/s0092-8674(85)80049-0. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Richards A. L., Okuno T., Takagaki Y., Djeu J. Y. Natural cytotoxic cell-specific cytotoxic factor produced by IL-3-dependent basophilic/mast cells. Relationship to TNF. J Immunol. 1988 Nov 1;141(9):3061–3066. [PubMed] [Google Scholar]
  36. Rollins B. J., Morrison E. D., Stiles C. D. Cloning and expression of JE, a gene inducible by platelet-derived growth factor and whose product has cytokine-like properties. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3738–3742. doi: 10.1073/pnas.85.11.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rollins B. J., Morrison E. D., Stiles C. D. Cloning and expression of JE, a gene inducible by platelet-derived growth factor and whose product has cytokine-like properties. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3738–3742. doi: 10.1073/pnas.85.11.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Schrader J. W., Crapper R. M. Autogenous production of a hemopoietic growth factor, persisting-cell-stimulating factor, as a mechanism for transformation of bone marrow-derived cells. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6892–6896. doi: 10.1073/pnas.80.22.6892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sherry B., Tekamp-Olson P., Gallegos C., Bauer D., Davatelis G., Wolpe S. D., Masiarz F., Coit D., Cerami A. Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta. J Exp Med. 1988 Dec 1;168(6):2251–2259. doi: 10.1084/jem.168.6.2251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Siraganian R. P., Siragania P. A. Mechanism of action of concanavalin A on human basophils. J Immunol. 1975 Feb;114(2 Pt 2):886–893. [PubMed] [Google Scholar]
  41. Wilson S. D., Burd P. R., Billings P. R., Martin C. A., Dorf M. E. The expression and regulation of a potential lymphokine gene (TCA3) in CD4 and CD8 T cell clones. J Immunol. 1988 Sep 1;141(5):1563–1570. [PubMed] [Google Scholar]
  42. Wolpe S. D., Davatelis G., Sherry B., Beutler B., Hesse D. G., Nguyen H. T., Moldawer L. L., Nathan C. F., Lowry S. F., Cerami A. Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties. J Exp Med. 1988 Feb 1;167(2):570–581. doi: 10.1084/jem.167.2.570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wong P. M., Humphries R. K., Chen T. R., Eaves C. J. Evidence for a multistep pathogenesis in the generation of tumorigenic cell lines from hemopoietic colonies exposed to Abelson virus in vitro. Exp Hematol. 1987 Mar;15(3):280–287. [PubMed] [Google Scholar]
  44. Yokota T., Lee F., Rennick D., Hall C., Arai N., Mosmann T., Nabel G., Cantor H., Arai K. Isolation and characterization of a mouse cDNA clone that expresses mast-cell growth-factor activity in monkey cells. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1070–1074. doi: 10.1073/pnas.81.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Young J. D., Liu C. C., Butler G., Cohn Z. A., Galli S. J. Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9175–9179. doi: 10.1073/pnas.84.24.9175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Zipfel P. F., Irving S. G., Kelly K., Siebenlist U. Complexity of the primary genetic response to mitogenic activation of human T cells. Mol Cell Biol. 1989 Mar;9(3):1041–1048. doi: 10.1128/mcb.9.3.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]

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