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. 1998 Jul;94(3):310–317.

Effects of nerve growth factor (NGF) and other fibroblast-derived growth factors on immature human mast cells (HMC-1).

P Welker 1, J Grabbe 1, A Grützkau 1, B M Henz 1
PMCID: PMC1364247  PMID: 9771435

Abstract

We have previously shown that fibroblast and keratinocyte supernatants up-regulate expression of mast cell characteristics in the human immature mast cell line HMC-1. This effect could not be induced in HMC-1 cells by the well-known mast cell growth factor stem cell factor (SCF), probably due to mutations of the SCF receptor c-Kit in these cells. Here we report the effects of several known fibroblast- and keratinocyte-derived growth factors, namely nerve growth factor (NGF), basic fibroblast growth factor, platelet-derived growth factor and transforming growth factor-beta, on mast cell differentiation, using HMC-1 cells as a model. NGF, at 0.1-50 ng/ml concentrations, caused a marked, dose-dependent up-regulation of tryptase, Fc epsilon RI and histamine within 10 days of culture, associated with an enhanced expression of mRNA for Fc epsilon RI and mast cell tryptase. On restriction analysis, only mast cell beta-tryptase, but not alpha-tryptase, could be demonstrated. Furthermore, the high-affinity NGF receptor (TrkA) was found at both the transcriptional and protein levels, while expression of the low-affinity NGF receptor was detectable at the mRNA level only. None of the other growth factors caused a significant alteration of the mast cell markers studied when added to HMC-1 cells at concentrations known to be biologically active in other culture systems. Immature human mast cells are thus induced to assume a more mature phenotype in vitro in response to NGF, most probably via stimulation of the high-affinity NGF receptor expressed on these cells. Besides SCF, NGF should therefore be considered as an additional mast cell growth factor that contributes to human mast cell maturation at tissue sites.

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Selected References

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

  1. Barker P. A., Shooter E. M. Disruption of NGF binding to the low affinity neurotrophin receptor p75LNTR reduces NGF binding to TrkA on PC12 cells. Neuron. 1994 Jul;13(1):203–215. doi: 10.1016/0896-6273(94)90470-7. [DOI] [PubMed] [Google Scholar]
  2. Bienenstock J., Tomioka M., Matsuda H., Stead R. H., Quinonez G., Simon G. T., Coughlin M. D., Denburg J. A. The role of mast cells in inflammatory processes: evidence for nerve/mast cell interactions. Int Arch Allergy Appl Immunol. 1987;82(3-4):238–243. doi: 10.1159/000234197. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Bothwell M. Tissue localization of nerve growth factor and nerve growth factor receptors. Curr Top Microbiol Immunol. 1991;165:55–70. doi: 10.1007/978-3-642-75747-1_4. [DOI] [PubMed] [Google Scholar]
  5. Broide D. H., Wasserman S. I., Alvaro-Gracia J., Zvaifler N. J., Firestein G. S. Transforming growth factor-beta 1 selectively inhibits IL-3-dependent mast cell proliferation without affecting mast cell function or differentiation. J Immunol. 1989 Sep 1;143(5):1591–1597. [PubMed] [Google Scholar]
  6. Butterfield J. H., Weiler D., Dewald G., Gleich G. J. Establishment of an immature mast cell line from a patient with mast cell leukemia. Leuk Res. 1988;12(4):345–355. doi: 10.1016/0145-2126(88)90050-1. [DOI] [PubMed] [Google Scholar]
  7. Czarnetzki B. M., Figdor C. G., Kolde G., Vroom T., Aalberse R., de Vries J. E. Development of human connective tissue mast cells from purified blood monocytes. Immunology. 1984 Mar;51(3):549–554. [PMC free article] [PubMed] [Google Scholar]
  8. Czarnetzki B. M., Grabbe J., Kolde G., Krüger-Krasagakes S., Welker P., Zuberbier T. Mast cells in the cytokine network: the what, where from and what for. Exp Dermatol. 1995 Aug;4(4 Pt 2):221–226. doi: 10.1111/j.1600-0625.1995.tb00249.x. [DOI] [PubMed] [Google Scholar]
  9. Czarnetzki B. M., Mecklenburg G. In vivo studies of factors influencing mast cell numbers in rat skin. J Dermatol Sci. 1991 Jan;2(1):1–8. doi: 10.1016/0923-1811(91)90036-w. [DOI] [PubMed] [Google Scholar]
  10. Davies A. M., Bandtlow C., Heumann R., Korsching S., Rohrer H., Thoenen H. Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. 1987 Mar 26-Apr 1Nature. 326(6111):353–358. doi: 10.1038/326353a0. [DOI] [PubMed] [Google Scholar]
  11. Deuel T. F. Polypeptide growth factors: roles in normal and abnormal cell growth. Annu Rev Cell Biol. 1987;3:443–492. doi: 10.1146/annurev.cb.03.110187.002303. [DOI] [PubMed] [Google Scholar]
  12. Furitsu T., Tsujimura T., Tono T., Ikeda H., Kitayama H., Koshimizu U., Sugahara H., Butterfield J. H., Ashman L. K., Kanayama Y. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J Clin Invest. 1993 Oct;92(4):1736–1744. doi: 10.1172/JCI116761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gabrilove J. L., Wong G., Bollenbacher E., White K., Kojima S., Wilson E. L. Basic fibroblast growth factor counteracts the suppressive effect of transforming growth factor-beta 1 on human myeloid progenitor cells. Blood. 1993 Feb 15;81(4):909–915. [PubMed] [Google Scholar]
  14. Gospodarowicz D. Biological activities of fibroblast growth factors. Ann N Y Acad Sci. 1991;638:1–8. doi: 10.1111/j.1749-6632.1991.tb49012.x. [DOI] [PubMed] [Google Scholar]
  15. Grabbe J., Welker P., Rosenbach T., Nürnberg W., Krüger-Krasagakes S., Artuc M., Fiebiger E., Henz B. M. Release of stem cell factor from a human keratinocyte line, HaCaT, is increased in differentiating versus proliferating cells. J Invest Dermatol. 1996 Aug;107(2):219–224. doi: 10.1111/1523-1747.ep12329664. [DOI] [PubMed] [Google Scholar]
  16. Gruber B. L., Marchese M. J., Kew R. R. Transforming growth factor-beta 1 mediates mast cell chemotaxis. J Immunol. 1994 Jun 15;152(12):5860–5867. [PubMed] [Google Scholar]
  17. Hamann K., Grabbe J., Welker P., Haas N., Algermissen B., Czarnetzki B. M. Phenotypic evaluation of cultured human mast and basophilic cells and of normal human skin mast cells. Arch Dermatol Res. 1994;286(7):380–385. doi: 10.1007/BF00371797. [DOI] [PubMed] [Google Scholar]
  18. Harvima I. T., Schechter N. M., Harvima R. J., Fräki J. E. Human skin tryptase: purification, partial characterization and comparison with human lung tryptase. Biochim Biophys Acta. 1988 Nov 2;957(1):71–80. doi: 10.1016/0167-4838(88)90158-6. [DOI] [PubMed] [Google Scholar]
  19. Herrmann J. L., Menter D. G., Hamada J., Marchetti D., Nakajima M., Nicolson G. L. Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of trkA. Mol Biol Cell. 1993 Nov;4(11):1205–1216. doi: 10.1091/mbc.4.11.1205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Horigome K., Bullock E. D., Johnson E. M., Jr Effects of nerve growth factor on rat peritoneal mast cells. Survival promotion and immediate-early gene induction. J Biol Chem. 1994 Jan 28;269(4):2695–2702. [PubMed] [Google Scholar]
  21. Huang S., Terstappen L. W. Lymphoid and myeloid differentiation of single human CD34+, HLA-DR+, CD38- hematopoietic stem cells. Blood. 1994 Mar 15;83(6):1515–1526. [PubMed] [Google Scholar]
  22. Kannan Y., Matsuda H., Ushio H., Kawamoto K., Shimada Y. Murine granulocyte-macrophage and mast cell colony formation promoted by nerve growth factor. Int Arch Allergy Immunol. 1993;102(4):362–367. doi: 10.1159/000236584. [DOI] [PubMed] [Google Scholar]
  23. Katz F. E., Michalevicz R., Lam G., Hoffbrand A. V., Goldman J. M. Effect of platelet-derived growth factor on enriched populations of haemopoietic progenitors from patients with chronic myeloid leukaemia. Leuk Res. 1987;11(4):339–344. doi: 10.1016/0145-2126(87)90178-0. [DOI] [PubMed] [Google Scholar]
  24. Keller J. R., Mantel C., Sing G. K., Ellingsworth L. R., Ruscetti S. K., Ruscetti F. W. Transforming growth factor beta 1 selectively regulates early murine hematopoietic progenitors and inhibits the growth of IL-3-dependent myeloid leukemia cell lines. J Exp Med. 1988 Aug 1;168(2):737–750. doi: 10.1084/jem.168.2.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Leon A., Buriani A., Dal Toso R., Fabris M., Romanello S., Aloe L., Levi-Montalcini R. Mast cells synthesize, store, and release nerve growth factor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3739–3743. doi: 10.1073/pnas.91.9.3739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lerner N. B., Nocka K. H., Cole S. R., Qiu F. H., Strife A., Ashman L. K., Besmer P. Monoclonal antibody YB5.B8 identifies the human c-kit protein product. Blood. 1991 May 1;77(9):1876–1883. [PubMed] [Google Scholar]
  27. Mahadeo D., Kaplan L., Chao M. V., Hempstead B. L. High affinity nerve growth factor binding displays a faster rate of association than p140trk binding. Implications for multi-subunit polypeptide receptors. J Biol Chem. 1994 Mar 4;269(9):6884–6891. [PubMed] [Google Scholar]
  28. Marshall J. S., Stead R. H., McSharry C., Nielsen L., Bienenstock J. The role of mast cell degranulation products in mast cell hyperplasia. I. Mechanism of action of nerve growth factor. J Immunol. 1990 Mar 1;144(5):1886–1892. [PubMed] [Google Scholar]
  29. Matsuda H., Coughlin M. D., Bienenstock J., Denburg J. A. Nerve growth factor promotes human hemopoietic colony growth and differentiation. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6508–6512. doi: 10.1073/pnas.85.17.6508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mazurek N., Weskamp G., Erne P., Otten U. Nerve growth factor induces mast cell degranulation without changing intracellular calcium levels. FEBS Lett. 1986 Mar 31;198(2):315–320. doi: 10.1016/0014-5793(86)80428-8. [DOI] [PubMed] [Google Scholar]
  31. Mekori Y. A., Metcalfe D. D. Transforming growth factor-beta prevents stem cell factor-mediated rescue of mast cells from apoptosis after IL-3 deprivation. J Immunol. 1994 Sep 1;153(5):2194–2203. [PubMed] [Google Scholar]
  32. Miller J. S., Westin E. H., Schwartz L. B. Cloning and characterization of complementary DNA for human tryptase. J Clin Invest. 1989 Oct;84(4):1188–1195. doi: 10.1172/JCI114284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nilsson G., Blom T., Kusche-Gullberg M., Kjellén L., Butterfield J. H., Sundström C., Nilsson K., Hellman L. Phenotypic characterization of the human mast-cell line HMC-1. Scand J Immunol. 1994 May;39(5):489–498. doi: 10.1111/j.1365-3083.1994.tb03404.x. [DOI] [PubMed] [Google Scholar]
  34. Nilsson G., Forsberg-Nilsson K., Xiang Z., Hallbök F., Nilsson K., Metcalfe D. D. Human mast cells express functional TrkA and are a source of nerve growth factor. Eur J Immunol. 1997 Sep;27(9):2295–2301. doi: 10.1002/eji.1830270925. [DOI] [PubMed] [Google Scholar]
  35. Pincelli C., Sevignani C., Manfredini R., Grande A., Fantini F., Bracci-Laudiero L., Aloe L., Ferrari S., Cossarizza A., Giannetti A. Expression and function of nerve growth factor and nerve growth factor receptor on cultured keratinocytes. J Invest Dermatol. 1994 Jul;103(1):13–18. doi: 10.1111/1523-1747.ep12388914. [DOI] [PubMed] [Google Scholar]
  36. Raffioni S., Bradshaw R. A., Buxser S. E. The receptors for nerve growth factor and other neurotrophins. Annu Rev Biochem. 1993;62:823–850. doi: 10.1146/annurev.bi.62.070193.004135. [DOI] [PubMed] [Google Scholar]
  37. Richard A., McColl S. R., Pelletier G. Interleukin-4 and nerve growth factor can act as cofactors for interleukin-3-induced histamine production in human umbilical cord blood cells in serum-free culture. Br J Haematol. 1992 May;81(1):6–11. doi: 10.1111/j.1365-2141.1992.tb08162.x. [DOI] [PubMed] [Google Scholar]
  38. Robertson M. W., Mehl V. S., Richards M. L., Liu F. T. mRNA variants encoding multiple forms of the high-affinity IgE receptor alpha subunit in transformed and nontransformed mast cells. Int Arch Allergy Appl Immunol. 1991;96(4):289–295. doi: 10.1159/000235511. [DOI] [PubMed] [Google Scholar]
  39. Santambrogio L., Benedetti M., Chao M. V., Muzaffar R., Kulig K., Gabellini N., Hochwald G. Nerve growth factor production by lymphocytes. J Immunol. 1994 Nov 15;153(10):4488–4495. [PubMed] [Google Scholar]
  40. Schadendorf D., Tiedemann K. H., Haas N., Czarnetzki B. M. Detection of human papillomaviruses in paraffin-embedded condylomata acuminata--comparison of immunohistochemistry, in situ hybridization, and polymerase chain reaction. J Invest Dermatol. 1991 Sep;97(3):549–554. doi: 10.1111/1523-1747.ep12481884. [DOI] [PubMed] [Google Scholar]
  41. Siraganian R. P. Refinements in the automated fluorometric histamine analysis system. J Immunol Methods. 1975 Jun;7(2-3):283–290. doi: 10.1016/0022-1759(75)90025-3. [DOI] [PubMed] [Google Scholar]
  42. Söderström S., Hallbök F., Ibáez C. F., Persson H., Ebendal T. Recombinant human beta-nerve growth factor (NGF): biological activity and properties in an enzyme immunoassay. J Neurosci Res. 1990 Dec;27(4):665–677. doi: 10.1002/jnr.490270427. [DOI] [PubMed] [Google Scholar]
  43. Tokunaga K., Nakamura Y., Sakata K., Fujimori K., Ohkubo M., Sawada K., Sakiyama S. Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers. Cancer Res. 1987 Nov 1;47(21):5616–5619. [PubMed] [Google Scholar]
  44. Tuveri M. A., Passiu G., Mathieu A., Aloe L. Nerve growth factor and mast cell distribution in the skin of patients with systemic sclerosis. Clin Exp Rheumatol. 1993 May-Jun;11(3):319–322. [PubMed] [Google Scholar]
  45. Ullrich A., Gray A., Berman C., Dull T. J. Human beta-nerve growth factor gene sequence highly homologous to that of mouse. Nature. 1983 Jun 30;303(5920):821–825. doi: 10.1038/303821a0. [DOI] [PubMed] [Google Scholar]
  46. 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]
  47. Walls A. F., Jones D. B., Williams J. H., Church M. K., Holgate S. T. Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase. J Pathol. 1990 Oct;162(2):119–126. doi: 10.1002/path.1711620204. [DOI] [PubMed] [Google Scholar]
  48. Welker P., Grabbe J., Czarnetzki B. M. Human keratinocytes release mast cell differentiation factors other than stem cell factor. Int Arch Allergy Immunol. 1995 May-Jun;107(1-3):139–141. doi: 10.1159/000236956. [DOI] [PubMed] [Google Scholar]
  49. Wiesner-Menzel L., Schulz B., Vakilzadeh F., Czarnetzki B. M. Electron microscopical evidence for a direct contact between nerve fibres and mast cells. Acta Derm Venereol. 1981;61(6):465–469. doi: 10.2340/0001555561465469. [DOI] [PubMed] [Google Scholar]
  50. Wilson E. L., Rifkin D. B., Kelly F., Hannocks M. J., Gabrilove J. L. Basic fibroblast growth factor stimulates myelopoiesis in long-term human bone marrow cultures. Blood. 1991 Mar 1;77(5):954–960. [PubMed] [Google Scholar]
  51. Xia H. Z., Kepley C. L., Sakai K., Chelliah J., Irani A. M., Schwartz L. B. Quantitation of tryptase, chymase, Fc epsilon RI alpha, and Fc epsilon RI gamma mRNAs in human mast cells and basophils by competitive reverse transcription-polymerase chain reaction. J Immunol. 1995 May 15;154(10):5472–5480. [PubMed] [Google Scholar]

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