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Co-Cultured Human Mast Cells Stimulate Fibroblast-Mediated Contraction of Collagen Gels

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Abstract

In the current study, we asked whether mast cells might modulate remodeling of extracellular matrix by affecting fibroblast-mediated contraction of three-dimensional collagen gels. Mast cells and human lung fibroblasts were co-cultured in floating type I collagen gels. The area of the gels was measured by an image analyzer. Mast cells in co-culture augmented fibroblast contractility (P < 0.001) in a timeand concentration dependent manner. The tryptase inhibitor bis(5-amidino-2-benzimidazo-lyl)methane (BABIM) were unable to block the augmented fibroblast contractility induced by co-cultured mast cells and tryptase added alone in the culture system had no effect on contractility, suggesting that other mediators besides tryptase might be involved. The amount of collagen in dissolved gels, measured as hydroxyproline, did not change after co-culture indicating that degradation of collagen may not be a major mechanism. Our findings support the hypothesis that the activity of mast cells may drive rearrangement of extracellular matrix and this and could subsequently lead to fibrosis and tissue dysfunction.

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References

  1. Rennard, S. I. 1996. Repair mechanisms in asthma. J. Allergy Clin. Immunol. 98:S278–S286.

    Google Scholar 

  2. Weibel, E. R., and R. G. Crystal. 1997. Structural organization of the pulmonary interstitium. In: R. G. Crystal, J. B. West, E. R. Weibel, P. J. Barnes, Eds. The Lung: Scientific Foundations, 2nd edition. Lippincott-Raven, Philadelphia Pennsylvania.

    Google Scholar 

  3. Sime, P. J., G. M. Tremblay, Z. Xing, B. O. Särnstrand, and J. Gauldie. 1997. Interstitial and bronchial fibroblasts. In: P. J. Barnes, M. M. Grunstein, A. R. Leff, A. J. Woolcock, Eds. Asthma. Lippincott-Raven, Philadelphia Pennsylvania.

    Google Scholar 

  4. Sköld, C. M., X. D. Liu, T. Umino, Y. K. Zhu, Y. Ohkuni, D. J. Romberger, J. R. Spurzem, A. J. Heires, and S. I. Rennard. 1999. Human neutrophil elastase augments contraction of released collagen gels. Am. J. Respir. Crit. Care Med. 159:1138–1146.

    Google Scholar 

  5. Zhang, H., M. Gharaee-Kermani, and S. H. Phan. 1997. Regulation of lung fibroblast alpha-smooth muscle actin expression, contractile phenotype and apoptosis by IL-1beta. J. Immunol. 158:1392–1399.

    Google Scholar 

  6. Hawkins, R. A., H. N. Claman, A. F. Clark, and J. C. Steigerwald. 1985. Increased dermal mast cell populations in progressive systemic sclerosis: a link in chronic fibrosis. Ann. Intern. Med. 102:182.

    Google Scholar 

  7. L. Bjermer, O. Bäck, G. Roos, and M. Thunell. 1986. Mast cells and lysozyme positive macrophage in bronchoalveolar lavage from patients with sarcoidosis. Acta. Med. Scand. 220:161–166.

    Google Scholar 

  8. Walls, A. F., A. R. Bennett, R. C. Godfrey, S. T. Holgate, and M. K. Church. 1991. Mast cell tryptase and histamine concentrations in bronchoalveolar lavage fluid from patients with interstitial lung diseases. Clin. Sci. 81:183.

    Google Scholar 

  9. Eklund, A., M. Van Hage-Hamsten, C. M. Sköld, and S. G. O. Johansson. 1993. Elevated levels of tryptase in bronchoalveolar lavage fluid from patients with sarcoidosis. Sarcoidosis 10:12–17.

    Google Scholar 

  10. Berlin Öhrn, M., C. M. Sköld, M. Van Hage-Hamsten, O. Zetterstr öm, and A. Eklund. 1995. Sarcoidosis patients have bronchial hyperreactivity and signs of mast cell activation in their bronchoalveolar lavage. Respiration 62:136–142.

    Google Scholar 

  11. Gruber, B. L., R. B. Kew, A. Jelaska, M. J. Marchese, J. Garlick, S. Ren, L. B. Schwartz, and J. H. Korn. 1997. Human mast cells activate fibroblasts, J. Immunol. 158:2310–2317.

    Google Scholar 

  12. Gruber, B. L., L. B. Schwartz, N. S. Ramamurthy, A. M. Irani, and M. J. Marchese. 1988. Activation of latent rheumatiod synovial collagenease by human mast cell tryptase. J. Immunol. 140:3936–3942.

    Google Scholar 

  13. Elsdale, T., and J. Bard. 1993. Collagen substrata for analysis of cell behavior. J. Cell Biol. 54:626–637.

    Google Scholar 

  14. Butterfield, J. H., D. A. Weiler, L. W. Hunt, S. R. Wynn, and P. C. Roche. 1990. Purification of tryptase from a human mast cell line. J. Leukocyte Biol. 47:409.

    Google Scholar 

  15. Bell, E., B. Ivarsson, and C. Merrill. 1979. Production of a tissuelike structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc. Natl. Acad. Sci. U.S.A. 76:1274–1278.

    Google Scholar 

  16. Bergman, I., and R. Loxley. 1963. Two improved and simplified methods for the spectrophotometric determination of hydroxyproline. Anal. Chem. 35: 1961–1965.

    Google Scholar 

  17. Ruoss, S. J., T. Hartmann, and G. H. Caughey. 1991. Mast cell tryptase is a mitogen for cultured fibroblasts. J. Clin. Invest. 88: 493–499.

    Google Scholar 

  18. Abe, M., M. Kurosawa, O. Ishikawa, Y. Miyachi, and H. Kido. 1998. Mast cell tryptase stimulates both human dermal fibroblast proliferation and type I collagen production. Clin. Exp. Allergy 28(12): 1509–1517.

    Google Scholar 

  19. Smith, T. J., and S. J. Parikh. 1999. HMC-1 mast cells active human orbital fibroblasts in co-culture: evidence for up-regulation of prostaglandin E2 and hyaluronan synthesis. Endocrinology 140(8): 3518–3525.

    Google Scholar 

  20. Algermissen, B., B. Hermes, I. Feldmann-Boeddeker, F. Bauer, B. M. Henz. 1999. Mast cell chymase and tryptase during tissue turnover: analysis on in vitro mitogenesis of fibroblasts and keratinocytes and alterations in cutaneous scar. Exp. Dermatol. 8(3): 193–198.

    Google Scholar 

  21. Gullberg, D., A. TingstrÖm, and C. A. Thuresson. 1990. Beta1 integrin mediated collagen gel contraction is stimulated by PDGF. Exp. Cell Res. 186: 264–272.

    Google Scholar 

  22. Montesano, R., and L. Orci. 1988. Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: Implication for wound healing. Proc. Natl. Acad. Sci. U.S.A. 85: 4894–4897.

    Google Scholar 

  23. Schwartz, L. B., R. A., Lewis, and K. F. Austen. 1981. Tryptase from human pulmonary mast cells. Purification and characterization. J. Biol. Chem. 256: 11939–11943.

    Google Scholar 

  24. Zhang, J., B. L. Gruber, M. J. Marchese, S. Zucker, L. B. Schwartz, and R. R. Kew. 1999. Mast cell tryptase does not alter matrix metalloproteinase expression in human dermal fibroblasts: further evidence that proteolytically active tryptase is a potent fibrogenic factor. J. Cell Physiol. 181(2): 312–318.

    Google Scholar 

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Sköld, C.M., Ohkuni, Y., Liu, X.D. et al. Co-Cultured Human Mast Cells Stimulate Fibroblast-Mediated Contraction of Collagen Gels. Inflammation 25, 47–51 (2001). https://doi.org/10.1023/A:1007075628316

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