Archives of Dermatological Research

, Volume 300, Supplement 1, pp 69–76 | Cite as

Mast cell tryptase and photoaging: possible involvement in the degradation of extra cellular matrix and basement membrane proteins

  • Arunasiri IddamalgodaEmail author
  • Quang Trong Le
  • Kenichi Ito
  • Kiyotaka Tanaka
  • Hiroyuki Kojima
  • Hiroshi Kido
Original Paper


Mast cells are widely distributed in the connective tissue of the body, but are particularly prominent in tissues such as skin. An increased number of mast cells can be found in the dermis under inflammatory conditions and ultraviolet (UV) exposed skin. Previous investigations have identified matrix metalloproteinases (MMPs) as key enzymes in the degradation of extra cellular matrix (ECM). This study reports about the potential contribution of human mast cell tryptase as a new triggering enzyme in matrix degradation process. Recent studies suggest that mast cell-derived proteases can activate MMPs. We investigated both the degradation of cellular matrix components and activation of MMPs by human tryptase. Mast cells are increased in photoaged skin and the increase of mast cell tryptase in UV irradiated skin was confirmed. Human mast cell tryptase was purified from human tonsils by a series of standard chromatographic procedures. Degradation of collagen type I was achieved by incubation of human type I collagen with tryptase and the fragments were quantified by SDS-PAGE and staining with Coomassie Brilliant Blue 250-R (CBB). Treatment with tryptase resulted in the activation of proMMP-9 as revealed by gelatinolytic activity in type IV collagen zymography. When tryptase was incubated with human type IV collagen, gradual degradation of intact collagen was detected by Western blotting. Furthermore, type IV collagen degradation was observed in the basement membrane (BM) of a three-dimensional (3D) skin model. Degranulation of mast cells, which release tryptase, can activate MMPs and causes direct damage to ECM proteins. These findings strongly implicate that tryptase either alone or in conjunction with activation of MMPs, can participate in ECM damage and the possible destruction of BM leading to photoaging.


Tryptase Collagen MMP Mast cells Photoaging 







Extra cellular matrix


Coomassie brilliant blue 250-R


Basement membrane


Conflict of interest statement

None of the authors has any potential conflict of interest.


  1. 1.
    Algermissen B, Laubscher JC, Bauer F, Henz BM (1999) Purification of mast cell proteases from murine skin. Exp Dermatol 8:413–418PubMedCrossRefGoogle Scholar
  2. 2.
    Bosset S, M.Bonnet-Duquennoy M, Barre P, Chalon A, Kurfurst R, Bonte F, Schnebert S, Le Varlet, Nicolas JF (2003) Photoaging shows histological features of chronic skin inflammation without clinical and molecular abnormalities. Br J Dermatol 149:826–835PubMedCrossRefGoogle Scholar
  3. 3.
    C1ompton SJ, Cairns JA, Holgate ST, Walls AF (1998) The role of mast cell tryptase in regulating endothelial cell proliferation, cytokine release, and adhesion molecule expression: typtase induces expression of mRNA for IL-1beta and IL-8 and stimulates the selective release of IL-8 from human umblical vein endothelial cells. J Immunol 161:1939–1946Google Scholar
  4. 4.
    Cottrel GS, Amadesi S, Schmidlin F, Bunnet N (2003) Protease activated receptor 2 activation, signaling and function. Biochem Soc Trans 31:1191–1197CrossRefGoogle Scholar
  5. 5.
    Fajardo I, Pejler G (2003) Human mast cell tryptase is a gelatinase. J Immunol 171:1493–1499PubMedGoogle Scholar
  6. 6.
    Gruber BL, Marchese MJ, Suzuki K, Schwartz LB, Okada Y, Nagase H, Ramamurthy NS (1989) Synovial procollagenase activation by human mast cell tryptase: dependence upon matrix metalloproteinase 3 activation. J Clin Invest 84:1657–1662PubMedCrossRefGoogle Scholar
  7. 7.
    Hallgren J, Pejler G (2006) Biology of mast cell tryptase- an inflammatory mediator. FEBS 273:1871–1895CrossRefGoogle Scholar
  8. 8.
    Hart PH, Grimbaldeston MA, Swift GJ, Jaksic A, Noonan FP, Finlay-Jones JJ (1998) Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity response in mice. J Exp Med 187:2045–2053PubMedCrossRefGoogle Scholar
  9. 9.
    Harvima RJ, Harvima IT, Diana Dull, Dunder UK, Schwartz LB (1998) Identification and characterization of multiple forms of tryptase from human mast cells. Arch Dermatol Res 291:73–80CrossRefGoogle Scholar
  10. 10.
    He SH, Chen P, Chen HQ (2003) Modulation of enzymatic activity of human mast cell tryptase and chymase by protease inhibitors. Acta Pharmacol Sin 24(9):923–929PubMedGoogle Scholar
  11. 11.
    He S, Gaca MD, Walls AF (1998) A role for tryptase in the activation of human mast cells: modulation of histamine release by tryptase and inhibitors of tryptase. J Pharmacol Exp Ther 286:289–297PubMedGoogle Scholar
  12. 12.
    Heussen C, Dowle EB (1980) Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing containing sodium dodecyl sulphate and co polymerized substrates. Anal Biochem 102:196–202PubMedCrossRefGoogle Scholar
  13. 13.
    Inomata S, Matsunaga Y, Amano S, Takada K, Kobayashi K, Tsunenaga M, Nishiyama T, Kohno Y, Fukuda M (2003) Possible involvement of gelatinases in basement membrane damage and wrinkle formation in chronically ultraviolet B-exposed hairless mouse. J Invest Dermatol 12:0–7Google Scholar
  14. 14.
    Jenkins G (2002) Molecular mechanisms of skin ageing and development. Mech Ageing Dev 123:801–810PubMedCrossRefGoogle Scholar
  15. 15.
    Johnson JL, Jackson CL, Angelini GP, George SJ (1998) Activation of matrix-degrading metalloproteinases by mast cell proteases in atheroscllerotic plaques. Arterioscler Thromb Vasc Biol 18:1707–1715PubMedGoogle Scholar
  16. 16.
    Kambe N, Kambe M, Kochan JP, Schwartz LB (2001) Human skin-derived mast cells can proliferate while retaining their characteristic functional and protease phenotypes. Blood 97:2045–2052PubMedCrossRefGoogle Scholar
  17. 17.
    Kaminska R, Helisalmi P, Harvima JR, Naukkarinen A, Horsmaheimo M, Harvima IT (1999) Focal dermal–epidermal separation and fibronectin cleavage in basement membrane by human mast cell tryptase. J Invest Dermatol 113:567–573PubMedCrossRefGoogle Scholar
  18. 18.
    Katunuma N, Kido H (1988) Biological functions of serine proteases in mast cells in allergic inflammation. J Cell Biochem 38:291–301PubMedCrossRefGoogle Scholar
  19. 19.
    Kido H, Fukusen N, Katunuma N (1985) Chymotrypsin- and trypsin-type serine proteases in rat mast cells: properties and functions. Arch Biochem Biophys 239:436–43PubMedCrossRefGoogle Scholar
  20. 20.
    Kido H, Fukusen N, Katunuma N, Morita T, Iwanaga S (1985) Tryptase from rat mast cells converts bovine prothrombin to thrombin. Arch Biochem Biophys 132:613–9Google Scholar
  21. 21.
    Krejci NC, Knapp DM, Rudd RJ, Bauer EA, McGuire J (1992) Dermal mast cell granules bind interstitial procollagenase and collagenase. J Invest Dermatol 98:748–752PubMedCrossRefGoogle Scholar
  22. 22.
    Kronauer C, Eberlein-Konig B, Ring J, Behrendt H (2003) Influence of UVB, UVA, and UVA1 irradiation on histamine release from human basophils and mast cells in vitro in the presence and absence of antioxidants. Photochem and Photobiol 77:531–534CrossRefGoogle Scholar
  23. 23.
    Little SS, Johnson DA (1995) Human mast cell tryptase isoforms: separation and examination of substrate-specificity differences. Biochem J immunol 307:341–346Google Scholar
  24. 24.
    Lohi J, Harvima I, Keski-Oja J (1992) Pericellular substrates of human mast cell tryptase. 72,000 dalton gelatinase and fibronectin. J Cell Biochem 50:337–349PubMedCrossRefGoogle Scholar
  25. 25.
    Okumura Y, Kudoh A, Takashima M, Inoue M, Sakai K, Kido H (1996) Purification and characterization of a novel isoform of mast cell tryptase from rat tongue. J Biochem 120:856–864PubMedGoogle Scholar
  26. 26.
    Peng Q, McEuen AR, Benyon RC, Walls AF (2003) The heterogeneity of mast cell tryptase from human lung and skin differences in size and substrate affinity. Eur J Biochem 270:270–283PubMedCrossRefGoogle Scholar
  27. 27.
    Pillai S, Oresajo C, Hayward J (2005) Ultraviolet radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation-a review. Int J Cosmet Sci 27:17–34CrossRefPubMedGoogle Scholar
  28. 28.
    Rojas IG, Martinez A, Pineda A, Spencer ML, Jimenez M, Rudolph MI (2004) Increased mast cell density and protease content in actinic cheilitis. J Oral Pathol Med 33:567–73PubMedCrossRefGoogle Scholar
  29. 29.
    Schwartz E (1988) Connective tissue alterations in the skin of ultraviolet irradiated hairless mice. J Invest Dermatol 91:158–161PubMedCrossRefGoogle Scholar
  30. 30.
    Schwartz LB, Irani AM, Roller K, Castells MC, schechter NM (1987) Quantitation of histamine, tryptase, and chymase in dispersed human T and TC mast cells. J Immunol 138:2611–2615PubMedGoogle Scholar
  31. 31.
    Schwartz LB (1995) Tryptase: a mast cell serine protease. In: Caughey GH (ed) Mast cell protease in immunology and biology. Marcel Dekker, New York, pp 88–101Google Scholar
  32. 32.
    Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi A, Bunnet NW (2000) Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med 6:151–158PubMedCrossRefGoogle Scholar
  33. 33.
    Stubbs MT, Morenweisers R, Sturzebecher J, Bauer M, Wolfarm B, Huber R, Piechottka GP, Matschiners G, Sommerhoffs, Fritz H, Auerswald EA (1997) The three-dimensional structure of recombinant leech-derived tryptase inhibitor in complex with trypsin. J Biol Chem 272:19931–1993PubMedCrossRefGoogle Scholar
  34. 34.
    Suzuki K, Lees M, Newland GF, Nagase H, Wooley DE (1995) Activation of precursors for matrix metalloproteinases 1 (interstitial collagenase) and 3 (stromelysin) by rat mast-cell proteinases I and II. Biochem J 305:301–306PubMedGoogle Scholar
  35. 35.
    Tanaka K, Hasegawa H, Asamitsu K, Okamoto T (2005) Prevention of the ultraviolet B-mediated skin photoaging by a nuclear factor kB inhibitor, parthenolide. J Pharmacol Exp Ther 315:624–630Google Scholar
  36. 36.
    Vayalil PK, Mittal A, Hara Y, Elmets CA, Katiyar SK (2004) Green tea polyphenols prevent ultraviolet light-induced oxidative damage and matrix metalloproteinases expression in mouse skin. J Invest Dermatol 122:1480–1487PubMedCrossRefGoogle Scholar
  37. 37.
    Walls AF (2000) Structure and Function of Mast Cell Tryptase. In: Marone G, Lichtenstein LM, Galli SJ (eds) Mast Cells and Basophils. Academic Press Harcourt publishers, San Diego, pp 291–309Google Scholar
  38. 38.
    Watson RE, Griffiths CE (2005) Pathogeneic aspects of cutaneous photoaging. J Cosmet Dermatol 4:230–236PubMedCrossRefGoogle Scholar
  39. 39.
    Yaar M, Eller MS, Gilchrest BA (2002) Fifty years of skin aging. J Invest Dermatol 7:51–58CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Arunasiri Iddamalgoda
    • 1
    Email author
  • Quang Trong Le
    • 2
  • Kenichi Ito
    • 1
  • Kiyotaka Tanaka
    • 1
  • Hiroyuki Kojima
    • 1
  • Hiroshi Kido
    • 2
  1. 1.Department of Research and Development Ichimaru Pharcos Co. LtdMotosu CityJapan
  2. 2.Institute of Enzyme ChemistryUniversity of TokushimaTokushimaJapan

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