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J Exp Med. 1989 July 1; 170(1): 245–257.
PMCID: PMC2189362

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


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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  • Metcalf D, Begley CG, Johnson GR, Nicola NA, Lopez AF, Williamson DJ. Effects of purified bacterially synthesized murine multi-CSF (IL-3) on hematopoiesis in normal adult mice. Blood. 1986 Jul;68(1):46–57. [PubMed]
  • 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. [PubMed]
  • Lee F, Yokota T, Otsuka T, Meyerson P, Villaret D, Coffman R, Mosmann T, Rennick D, Roehm N, Smith C, et al. 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. [PubMed]
  • Bottomly K. A functional dichotomy in CD4+ T lymphocytes. Immunol Today. 1988 Sep;9(9):268–274. [PubMed]
  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. 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]
  • Paul WE, Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. [PubMed]
  • Nabel G, Galli SJ, Dvorak AM, Dvorak HF, Cantor H. Inducer T lymphocytes synthesize a factor that stimulates proliferation of cloned mast cells. Nature. 1981 May 28;291(5813):332–334. [PubMed]
  • Galli SJ, Dvorak AM, Marcum JA, Ishizaka T, Nabel G, Der Simonian H, Pyne K, Goldin JM, Rosenberg RD, Cantor H, et al. Mast cell clones: a model for the analysis of cellular maturation. J Cell Biol. 1982 Nov;95(2 Pt 1):435–444. [PMC free article] [PubMed]
  • Young JD, Liu CC, Butler G, Cohn ZA, Galli SJ. 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. [PubMed]
  • Schrader JW, Crapper RM. 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. [PubMed]
  • Wong PM, Humphries RK, Chen TR, Eaves CJ. 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]
  • Chung SW, Wong PM, Shen-Ong G, Ruscetti S, Ishizaka T, Eaves CJ. Production of granulocyte-macrophage colony-stimulating factor by Abelson virus-induced tumorigenic mast cell lines. Blood. 1986 Nov;68(5):1074–1081. [PubMed]
  • Brown MA, Pierce JH, Watson CJ, Falco J, Ihle JN, Paul WE. B cell stimulatory factor-1/interleukin-4 mRNA is expressed by normal and transformed mast cells. Cell. 1987 Aug 28;50(5):809–818. [PubMed]
  • Pierce JH, Di Fiore PP, Aaronson SA, Potter M, Pumphrey J, Scott A, Ihle JN. Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanism. Cell. 1985 Jul;41(3):685–693. [PubMed]
  • Humphries RK, Abraham S, Krystal G, Lansdorp P, Lemoine F, Eaves CJ. Activation of multiple hemopoietic growth factor genes in Abelson virus-transformed myeloid cells. Exp Hematol. 1988 Oct;16(9):774–781. [PubMed]
  • Richards AL, Okuno T, Takagaki Y, Djeu JY. 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]
  • Rennick DM, Lee FD, Yokota T, Arai KI, Cantor H, Nabel GJ. A cloned MCGF cDNA encodes a multilineage hematopoietic growth factor: multiple activities of interleukin 3. J Immunol. 1985 Feb;134(2):910–914. [PubMed]
  • Kaye J, Porcelli S, Tite J, Jones B, Janeway CA., 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. [PMC free article] [PubMed]
  • Liu FT, Bohn JW, Ferry EL, Yamamoto H, Molinaro CA, Sherman LA, Klinman NR, Katz DH. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol. 1980 Jun;124(6):2728–2737. [PubMed]
  • Galli SJ, Dvorak AM, Marcum JA, Nabel G, Goldin JM, Rosenberg RD, Cantor H, Dvorak HF. Mouse mast cell clones: modulation of functional maturity in vitro. Monogr Allergy. 1983;18:166–170. [PubMed]
  • Dvorak AM, Galli SJ. Antigen-induced, IgE-mediated degranulation of cloned immature mast cells derived from normal mice. Am J Pathol. 1987 Mar;126(3):535–545. [PubMed]
  • Wilson SD, Burd PR, Billings PR, Martin CA, Dorf ME. 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]
  • Freeman GJ, Clayberger C, DeKruyff R, Rosenblum DS, 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. [PubMed]
  • Lomedico PT, Gubler U, Hellmann CP, Dukovich M, Giri JG, Pan YC, Collier K, Semionow R, Chua AO, Mizel SB. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature. 312(5993):458–462. [PubMed]
  • 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. [PubMed]
  • Rollins BJ, Morrison ED, Stiles CD. 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. [PubMed]
  • Gough NM, Gough J, Metcalf D, Kelso A, Grail D, Nicola NA, Burgess AW, Dunn AR. Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte-macrophage colony stimulating factor. Nature. 309(5971):763–767. [PubMed]
  • Davatelis G, Tekamp-Olson P, Wolpe SD, 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. [PMC free article] [PubMed]
  • Brown KD, Zurawski SM, Mosmann TR, 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]
  • Sherry B, Tekamp-Olson P, Gallegos C, Bauer D, Davatelis G, Wolpe SD, 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. [PMC free article] [PubMed]
  • Burd PR, Freeman GJ, Wilson SD, Berman M, DeKruyff R, Billings PR, Dorf ME. Cloning and characterization of a novel T cell activation gene. J Immunol. 1987 Nov 1;139(9):3126–3131. [PubMed]
  • Campos-Neto A, Stashenko PP. Interleukin 1 and T-cell activation. Immunol Today. 1988 May;9(5):131–131. [PubMed]
  • Nordan RP, Pumphrey JG, 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]
  • Zipfel PF, Irving SG, 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. [PMC free article] [PubMed]
  • Siraganian RP, Siragania PA. Mechanism of action of concanavalin A on human basophils. J Immunol. 1975 Feb;114(2 Pt 2):886–893. [PubMed]
  • Bach MK, Brashler JR. Inhibition of IgE and compound 48/80-induced histamine release by lectins. Immunology. 1975 Aug;29(2):371–386. [PubMed]
  • Burd PR, Rollins BJ, Wilson SD, Billings PR, Stiles CD, Dorf ME. Comparison of fibroblast and T-cell activation genes. Cell Immunol. 1988 Sep;115(2):481–483. [PubMed]
  • Rollins BJ, Morrison ED, Stiles CD. 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. [PubMed]
  • Wolpe SD, Davatelis G, Sherry B, Beutler B, Hesse DG, Nguyen HT, Moldawer LL, Nathan CF, Lowry SF, 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. [PMC free article] [PubMed]
  • Davatelis G, Wolpe SD, Sherry B, Dayer JM, Chicheportiche R, Cerami A. Macrophage inflammatory protein-1: a prostaglandin-independent endogenous pyrogen. Science. 1989 Feb 24;243(4894 Pt 1):1066–1068. [PubMed]
  • Furutani Y, Nomura H, Notake M, Oyamada Y, Fukui T, Yamada M, Larsen CG, Oppenheim JJ, 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. [PubMed]
  • Kurt-Jones EA, Hamberg S, Ohara J, Paul WE, Abbas AK. Heterogeneity of helper/inducer T lymphocytes. I. Lymphokine production and lymphokine responsiveness. J Exp Med. 1987 Dec 1;166(6):1774–1787. [PMC free article] [PubMed]
  • Coffman RL, Seymour BW, Lebman DA, Hiraki DD, Christiansen JA, Shrader B, Cherwinski HM, Savelkoul HF, Finkelman FD, Bond MW, et al. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev. 1988 Feb;102:5–28. [PubMed]
  • Coffman RL, 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]
  • Ishizaka T, White JR, Saito H. Activation of basophils and mast cells for mediator release. Int Arch Allergy Appl Immunol. 1987;82(3-4):327–332. [PubMed]
  • Burnet FM. The probable relationship of some or all mast cells to the T-cell system. Cell Immunol. 1977 May;30(2):358–360. [PubMed]

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