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Skin-derived antileukoproteinase (SKALP) is decreased in pustular forms of psoriasis. A clue to the pathogenesis of pustule formation?

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Abstract

Skin-derived antileukoproteinase (SKALP, also known as elafin) is an inducible epidermal serine proteinase inhibitor, that we have recently characterized at the protein and DNA levels. SKALP is a strong and specific inhibitor of PMN elastase, and is putatively involved in the regulation of cutaneous inflammatory processes. In order to investigate the role of SKALP in the control of elastase in psoriatic epidermis, we compared SKALP expression in normal skin, and in skin from patients with chronic plaque psoriasis and pustular forms of psoriasis. Epidermal scales and biopsies were collected and SKALP expression was studied at the mRNA level and at the protein level both functionally and immunochemically. In epidermal scales, we found that the levels of both free and total SKALP activity in pustular psoriasis were far lower than in plaque psoriasis. A significant number of pustular psoriasis patients showed latent SKALP activity, which represents the amount of SKALP putatively complexed to elastase. In addition, we found free elastase activity in 25% of the pustular psoriasis patients, indicating a total saturation of epidermal SKALP activity. In epidermal biopsies from pustular psoriasis patients, SKALP activity was significantly decreased compared with those from plaque psoriasis patients. Northern blot analysis did not reveal differences in epidermal mRNA levels between chronic plaque psoriasis and pustular psoriasis. We hypothesize that a reduced amount of epidermal SKALP contributes to an imbalance between elastase and its inhibitor, thereby promoting the formation of epidermal pustules. We suggest that these findings could provide a rationale for the treatment of pustular psoriasis with inhibitors of PMN-derived proteinases, as a new therapeutic modality.

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References

  1. Kerkhof PCM van de (1986) Clinical features. In: Mier PD, Kerkhof PCM van de (eds) Textbook of psoriasis. Churchill Livingstone, Edinburgh, pp 13–39

    Google Scholar 

  2. Elder JT, Fisher GJ, Lindquist PB, Bennett GL, Pittelkow MR, Coffey J, Ellingsworth L, Derynck R, Voorhees JJ (1989) Overexpression of transforming growth factor in psoriatic epidermis. Science 243:811–814

    Article  PubMed  CAS  Google Scholar 

  3. Baadsgaard O, Tong P, Elder JT, Hansen ER, Ho V, Hammerberg C, Lange-Vejlsgaard G, Fox DA, Fisher G, Chan LS, Voorhees JJ, Cooper KD (1990) UM4D4+(Cdw60) T cells are compartmentalized into psoriatic skin and release lymphokines that induce a keratinocyte phenotype expressed in psoriatic lesions. J Invest Dermatol 95:275–282

    Article  PubMed  CAS  Google Scholar 

  4. Uyemura K, Yamamura M, Fivenson DF, Modlin RL, Nickoloff BJ (1913) The cytokine network in lesional and lesionfree psoriatic skin is characterized by a T-helper type 1 cellmediated response. J Invest Dermatol 101:710–705

    Google Scholar 

  5. Kerkhof PCM van de, Chang A (1989) Migration of polymorphonuclear leukocytes in psoriasis. Skin Pharmacol 2: 138–154

    Article  PubMed  Google Scholar 

  6. Schalkwijk J, Chang A, Janssen P, Jongh GJ de, Mier PD (1990) Skin-derived antileucoproteinases (SKALPs): characterization of two new elastase inhibitors from psoriatic epidermis. Br J Dermatol 122:631–641

    Article  PubMed  CAS  Google Scholar 

  7. Schalkwijk J, Roo C de, Jongh GJ de (1991) Skin-derived antileukoproteinase (SKALP) an elastase inhibitor from human keratinocytes. Purification and biochemical properties. Biochem Biophys Acta 1096:148–154

    PubMed  CAS  Google Scholar 

  8. Schalkwijk J, Vlijmen-Willems IMJJ van, Alkemade JAC, Jongh GJ de (1993) Immunohistochemical localization of SKALP/elafin in psoriatic epidermis. J Invest Dermatol 100:390–393

    Article  PubMed  CAS  Google Scholar 

  9. Janoff A (1985) Elastases and emphysema. Current assement of the protease-antiprotease hypothesis. Am Rev Respir Dis 132:417–433

    PubMed  CAS  Google Scholar 

  10. Schalkwijk J, Berg WB van den, Putte LBA van de, Joosten LAB (1987) Elastase secreted by activated polymophonuclear leukocytes causes chondrocyte damage in intact articular cartilage: escape from inactivation by alpha-1 proteinase inhibitor. Br J Exp Pathol 68:81–88

    PubMed  CAS  Google Scholar 

  11. Schrijver G, Schalkwijk J, Robben JCM, Assman KJM, Koene RAP (1989) Antiglomerular basement membrane nephritis in beige mice. J Exp Med 169:1435–1448

    Article  PubMed  CAS  Google Scholar 

  12. Takamori K, Yoshike T, Morioka S, Ogawa H (1988) The role of proteases in the pathogenesis of bullous diseases. Int J Dermatol 27:533–539

    PubMed  CAS  Google Scholar 

  13. Briggaman RA, Schechter NM, Fräki J, Lazarus GS (1984) Degradation of the epidermal-dermal junction by proteolytic enzymes from human skin and human polymorphonuclear leukocytes. J Exp Med 160:1047–1042

    Article  Google Scholar 

  14. Wiedow O, Schröder J, 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 265:14791–14795

    PubMed  CAS  Google Scholar 

  15. Wiedow O, Lüdemann J, Utecht B (1991) Elafin is a potent inhibitor of proteinase 3. Biochem Biophys Res Commun 174: 6–10

    Article  PubMed  CAS  Google Scholar 

  16. Sallenave JM, Ryle AP (1991) Purification and characterization of elastase-specific inhibitor. Sequence homology with mucus proteinase inhibitor. Biol Chem Hoppe Seyler 372:13–21

    PubMed  CAS  Google Scholar 

  17. Alkemade H, Kerkhof P van de, Schalkwijk J (1992) Demonstration of skin-derived antileukoproteinase (SKALP) in urine of psoriatic patients. J Invest Dermatol 99:3–7

    Article  PubMed  CAS  Google Scholar 

  18. Alkemade HAC, 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 104:189–193

    Article  PubMed  CAS  Google Scholar 

  19. Molhuizen HOF, Alkemade HAC, Zeeuwen PLJM, Jongh GJ de, Wieringa B, Schalkwijk J (1993) SKALP/elafin: an elastase inhibitor from cultured human keratinocytes. Purification, cDNA sequence and evidence for transglutaminase crosslinking. J Biol Chem 268:12028–12032

    PubMed  CAS  Google Scholar 

  20. Saheki T, Ito F, Hagiwara H, Saito Y, Kuroki J, Tachibana S, Hirose S (1992) Primary structure of the human elafin precursor deduced from the nucleotide sequence of its gene and the presence of unique repetitive sequences in the prosegment. Biochem Biophys Res Commun 185:240–245

    Article  PubMed  CAS  Google Scholar 

  21. Molhuizen HOF, Zeeuwen PLJM, Olde Weghuis D, Geurts van Kessel A, Schalkwijk J (1994) Assignment of the human gene encoding the epidermal serine proteinase inhibitor SKALP (P13) to chromosome region 20q12–q13. Cytogenet Cell Genet 66:129–131

    Article  PubMed  CAS  Google Scholar 

  22. Sambrook J, Fritch EF, Maniatis T (1989) Molecular cloning, a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, New York

    Google Scholar 

  23. Streit V, Wiedow O, Bartels J, Christophers E (1993) Metabolism and urinary excretion of elafin, a specific inhibitor of human leukocyte elastase (abstract). J Invest Dermatol 101:422

    Google Scholar 

  24. Wiedow O, Wiese F, Christophers E, (1995) Lesional elastase activity in psoriasis. Diagnostic and prognostic significance. Arch Dermatol Res 287:632–635

    Article  PubMed  CAS  Google Scholar 

  25. Perlmutter DH, Joslin G, Nelson P, Schasteen C, Adams SP, Fallon RJ (1990) Endocytosis and degradation of alpha 1-antitrypsin-protease complexes is mediated by the serpin-enzyme complex (SEC)_receptor. J Biol Chem 265 (28):16713–16716

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, University Hospital Nijmegen, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands

    Astrid L. A. Kujipers, Patrick L. J. M. Zeeuwen, Gijs J. de Jongh, Peter C. M. van de Kerkhof, Hans A. C. Alkemade & Joost Schalkwijk

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  1. Astrid L. A. Kujipers
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  2. Patrick L. J. M. Zeeuwen
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  3. Gijs J. de Jongh
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  4. Peter C. M. van de Kerkhof
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  5. Hans A. C. Alkemade
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  6. Joost Schalkwijk
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Kujipers, A.L.A., Zeeuwen, P.L.J.M., de Jongh, G.J. et al. Skin-derived antileukoproteinase (SKALP) is decreased in pustular forms of psoriasis. A clue to the pathogenesis of pustule formation?. Arch Dermatol Res 288, 641–647 (1996). https://doi.org/10.1007/BF02505272

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  • DOI: https://doi.org/10.1007/BF02505272

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