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Archives of Dermatological Research

, Volume 288, Issue 8, pp 458–462 | Cite as

Expression of SKALP/elafin during wound healing in human skin

  • Bert H. van Bergen
  • Monique P. M. Andriessen
  • Karin I. J. Spruijt
  • Peter C. M. van de Kerkhof
  • Joost Schalkwijk
Original Paper

Abstract

Skin-derived antileukoproteinase (SKALP), also known as elafin, is a proteinase inhibitor with specificity for polymorphonuclear leucocyte (PMN)-derived elastase and proteinase-3. SKALP is absent in normal human epidermis, but is strongly induced in inflammatory dermatoses such as psoriasis. SKALP is putatively involved in the regulation of cutaneous inflammation by inhibiting PMN derived proteinases. The aim of this study was to investigate SKALP expression and PMN infiltration during wound healing in human skin. This was examined in healing excisional wounds in normal skin and in impaired healing in various types of chronic venous ulcers. Tissues were analysed using immunohistochemistry and Northern blot analysis. Healing of excisional wounds was studied from day 0 to day 14. An influx of PMN was seen rapidly after wounding and was maximal between day 2 and 4 and then subsided. SKALP was induced within 48 h and was expressed in the suprabasal keratinocytes of the wound edge and the migrating epidermal sheet. SKALP expression was maximal on day 4 and was downregulated at the time of complete reepithelialization (7–14 days). In venous ulcers, PMN were abundant in the wound bed and scarce under the wound edge. SKALP was strongly expressed in the keratinocytes of the wound edge in all types of ulcers studied. In the wound bed, SKALP was not detectable. Our results suggest that SKALP plays a role in the acute, inflammatory phase of wound healing. From the kinetics and topology of SKALP expression we surmise that it negatively regulates PMN infiltration.

Key words

SKALP Wound healing Antileukoproteinase Elastase 

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References

  1. 1.
    Alkemade H, Kerkhof P van de, Schalkqijk J (1992) Demonstration of skin-derived antileukoproteinase (SKALP) in urine of psoriatic patients. J Invest Dermatol 99:3–7PubMedCrossRefGoogle Scholar
  2. 2.
    Alkemade HA, Molhuizen HO, Vlijmen Willems IM van, Haelst UJ van, Schalkwijk J (1993) Differential expression of SKALP/elafin in human epidermal tumors. Am J Pathol 143: 1679–1687PubMedGoogle Scholar
  3. 3.
    Alkemade JAC, Molhuizen HOF, Ponec M, Kempenaar JA, Zeeuwen PLJM, Jongh GJ de, Vlijmen-Willems MJJ van, Erp PEJ van, Kerkhof PCM van de, Schalkwijk J (1994) SKALP/elafin is an inducible proteinase inhibitor in human epidermal keratinocytes. J Cell Sci 107:2335–2342PubMedGoogle Scholar
  4. 4.
    Alkemade JAC, Jongh GJ de, Arnold WP, Kerkhof PCM van de, Schalkwijk J (1995) Levels of skin-derived antileukoproteinase (SKALP)/elafin in serum correlate with disease activity during treatment of severe psoriasis with cyclosporin A. J Invest Dermatol 104:189–193PubMedCrossRefGoogle Scholar
  5. 5.
    Chang A, Schalkwijk J, Happle R, Kerkhof PC van de (1990) Elastase-inhibiting activity in scaling skin disorders. Acta Derm Venereol (Stockh) 70:147–151Google Scholar
  6. 6.
    Reference deletedGoogle Scholar
  7. 7.
    Clark RAF (1993) Mechanisms of cutaneous wound repair. In: Westerhof W (ed) Leg ulcers: diagnosis and treatment. Elsevier Science, Amsterdam, pp 29–50Google Scholar
  8. 8.
    Clark RA, Winn HJ, Dvorak HF, Colvin RB (1983) Fibronectin beneath reepithelializing epidermis in vivo: sources and significance. J Invest Dermatol [Suppl] 80:26s-30sPubMedCrossRefGoogle Scholar
  9. 9.
    Grinnell F, Zhu M (1994) Identification of neutrophil elastase as the proteinase in burn wound fluid responsible for degradation of fibronectin. J Invest Dermatol 103:155–161PubMedCrossRefGoogle Scholar
  10. 10.
    Grinnell F, Ho CH, Wysocki A (1992) Degradation of fibronectin and vitronectin in chronic wound fluid: analysis by cell blotting, immunoblotting, and cell adhesion assays. J Invest Dermatol 98:410–416PubMedCrossRefGoogle Scholar
  11. 11.
    Molhuizen HO, Alkemade HA, Zeeuwen PL, Jongh GJ de, Wieringa B, Schalkwijk J (1993) SKALP/elafin: an elastase inhibitor from cultured human keratinocytes. Purification, cDNA sequence, and evidence for transglutaminase cross-linking. J Biol Chem, 268:12028–12032PubMedGoogle Scholar
  12. 12.
    Molhuizen HO, Zeeuwen PL, Olde Weghuis D, Geurts van Kessel A, Schalkwijk J (1994) Assignment of the human gene encoding the epidermal serine proteinase inhibitor SKALP (PI3) to chromosome region 20q12→q13. Cytogenet Cell Genet 66:129–131PubMedCrossRefGoogle Scholar
  13. 13.
    Newman SL, Henson JE, Henson PM (1982) Phagocytosis of senescent neutrophils by human monocyte derived macrophages and rabbit inflammatory macrophages. J Exp Med 156: 430–442PubMedCrossRefGoogle Scholar
  14. 14.
    Saheki T, Ito F, Hagiwara H, Saito Y, Kuroki J, Tachibana S, Hirose S (1992) Primary structure of the human elafin precursor preproelafin deduced from the nucleotide sequence of its gene and the presence of unique repetitive sequences in the prosegment. Biochem Biophys Res Commun 185:240–245PubMedCrossRefGoogle Scholar
  15. 15.
    Sallenave JM, Ryle AP (1991) Purification and characterization of elastase-specific inhibitor. Sequence homology with mucus proteinase inhibitor. Biol Chem Hoppe Seyler 372:13–21PubMedGoogle Scholar
  16. 16.
    Sallenave J, Schullmann J, Crosley J, Jordana M, Gauldie J (1995) Regulation of secretory leukocyte proteinase inhibitor (SLPI) and elastase-specific inhibitor (ESI/elafin) in human airway epithelial cells by cytokines and neutrophilic enzymes. Am J Resp Cell Mol biol 11:733–741Google Scholar
  17. 17.
    Reference deletedGoogle Scholar
  18. 18.
    Schalkwijk J, Chang A, Janssen P, Jongh GJ de, Mier PD (1990) Skin-derived antileucoproteases (SKALPs): characterization of two new elastase inhibitors from psoriatic epidermis. Br J Dermatol 122:631–641PubMedCrossRefGoogle Scholar
  19. 19.
    Schalkwijk J, Roo C de, Jongh GJ de (1991) Skin-derived antileukoproteinase (SKALP), an elastase inhibitor from human keratinocytes. Purification and biochemical properties. Biochim Biophys Acta 1096:148–154PubMedGoogle Scholar
  20. 20.
    Schalkwijk J, Vlijmen IM van, Alkemade JA, Jongh GJ de (1993) Immunohistochemical localization of SKALP/elafin in psoriatic epidermis. J Invest Dermatol 100:390–393PubMedCrossRefGoogle Scholar
  21. 21.
    Tonnesen MG, Worthen GS, Johnston RB (1988) Neutrophil emigration, activation, and tissue damage. In: Clark RAF, Henson PM (eds) Molecular and cellular biology of wound repair. Plenum Press, New York, pp 149–183Google Scholar
  22. 22.
    Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365–376PubMedCrossRefGoogle Scholar
  23. 23.
    Wiedow O, Schroder JM, Gregory H, Young JA, Christophers E (1990) Elafin: an elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence. J Biol Chem 265:14791–14795PubMedGoogle Scholar
  24. 24.
    Wiedow O, Lüdemann J, Utecht B (1991) Elafin is a potent inhibitor of proteinase 3. Biochem Biophys Res Commun 174: 6–10PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Bert H. van Bergen
    • 1
  • Monique P. M. Andriessen
    • 1
  • Karin I. J. Spruijt
    • 1
  • Peter C. M. van de Kerkhof
    • 1
  • Joost Schalkwijk
    • 1
  1. 1.Department of DermatologyUniversity Hospital NijmegenNijmegenThe Netherlands

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