Secretory leukocyte protease inhibitor (SLPI) is a small, cationic protein that is known to be constitutively expressed by several glandular epithelia. SLPI inhibits leukocyte-derived proteinases, has anti-HIV-1, antibacterial, and anti-fungal properties, and interferes with the induction of synthesis of proinflammatory mediators in monocytes and macrophages. We now report that at both the mRNA and the protein level, SLPI shows inducible expression in a nonglandular epithelium. A weak expression of SLPI was found in the stratum granulosum of adult normal human epidermis; however, in lesional psoriatic epidermis and in migrating keratinocytes of healing wounds, a strong cytoplasmic staining was seen in the suprabasal keratinocytes. Remarkably, in the dermis adjacent to SLPI-expressing keratinocytes, SLPI was found extracellularly associated with elastin fibers, whereas the dermis in normal skin was negative. In cell culture, SLPI was hardly expressed in monolayers of proliferating keratinocytes. Differentiating cultures with a phenotype of normal skin expressed low levels of SLPI, whereas cultures with a regenerative/psoriatic phenotype expressed high levels. Functional studies with recombinant SLPI indicated that its antibacterial spectrum and potency are distinct from other anti-microbial peptides such as lysozyme and defensins. In view of the multiple functions of SLPI and the inducibility, we propose that it acts as an important first line defence mechanism in cutaneous injury.

I In adult human skin, the expression of the extracellular matrix glycoprotein tenascin is limited. Under hyperproliferative conditions such as psoriasis and epidermal tumours, dermal tenascin expression is strongly upregulated. The aim of this study was to investigate the pattern and kinetics of tenascin expression in human skin during wound healing and to address the question of whether keratinocytes can directly interact with tenascin during re-epithelialization. Tenascin expression was investigated in excisional wounds in normal human skin, in explants of normal human skin, and in chronic venous ulcers, using immunohistochemistry. No tenascin staining was found directly underneath the leading edge of the sheet of migrating keratinocytes in the excisional wounds and explants. In the excisional wounds and the ulcers, dermal tcnascin was strongly upregulated in areas adjacent to hyperproliferative epidermis. These hyperproliferative areas are located approximately 10-50 cells behind the leading edge, as assessed by staining for the Ki-67 antigen and the proliferating cell nuclear antigen (PCNA). At the later stages of normal wound healing and in the chronic ulcers, tenascin was also detected in the wound bed. In these areas, the dermal-epidermal junction stained positive for laminin but was negative for heparan sulphate. The absence of the latter basement membrane component suggests that the formation of a new basement membrane is not completed in these wounds. These findings suggest that tenascin is not a substrate for migrating keratinocytes; that the rapid induction of tenascin expression in the papillary dermis during wound healing results from interaction with the hyperproliferative epidermis; and that in the later stages of wound healing, keratinocytes can potentially interact with tenascin in the wound bed, because the basement membrane of the neo-epidermis is incomplete.

Skin-derived antileukoproteinase (SKALP), Key words SKALP • Wound healing • also known as elafin, is a proteinase inhibitor with Antileukoproteinase • Elastase specificity for polymorphonuclear leucocyte (PMN)-derived elastase and proteinase-3. SKALP is absent in normal human epidermis, but is strongly induced in Introduction inflammatory dermatoses such as psoriasis. SKALP is putatively involved in the regulation of cutaneous in-Proteinase activity is regulated systemically by numerous flammation by inhibiting PMN derived proteinases. plasma-derived inhibitors, such as a!-proteinase inhibitor The aim of this study was to investigate SKALP ex-and a 2-macroglobulin. However, in normal human epipression and PMN infiltration during wound healing dermis only low levels of antiproteinase activity directed in human skin. This was examined in healing exci-against the major polymorphonuclear leucocyte (PMN)-sional wounds in normal skin and in impaired healing derived proteinases (e.g. elastase, proteinase-3 and cathepin various types of chronic venous ulcers. Tissues were sin G) can be detected. Antiproteinase activity is upreguanalysed using immunohistocliemistry and Northern lated in inflammatory skin diseases such as psoriasis [5, blot analysis. Healing of excisional wounds was stud-18-20] and epidermal tumours [2]. In previous studies we ied from day 0 to day 14. An influx of PMN was seen and others have characterized this antiproteinase activity rapidly after wounding and was maximal between day and found it to be an inducible inhibitor of elastase and 2 and 4 and then subsided. SKALP was induced within proteinase 3 [23]. This inhibitor has been named skin-de-48 h and was expressed in the suprabasal keratino-rived antileukoproteinase (SKALP) [18], also known as cytes of the wound edge and the migrating epidermal elafin [23,24] or elastase-specific inhibitor (ESI) [15 |. sheet. SKALP expression was maximal on day 4 and Cloning of the SKALP cDNA and gene has revealed that was downregulated at the time of complete reepithe-the molecule contains several N-terminal transglutamilialization (7-14 days). In venous ulcers, PMN were nase substrate motifs, in addition to the antiproteinase doabundant in the wound bed and scarce under the main that was already known [11,12,14]. SKALP is a sewound edge. SKALP was strongly expressed in the creted molecule, and we have recently demonstrated its keratinocytes of the wound edge in all types of ulcers presence in urine and plasma of psoriatic patients [1,4]. studied. In the wound bed, SKALP was not detectable. Our results suggest that S SKALP may be involved in the regulation of euta-P plays a role in the neous animation by inhibiting PMN-derived o acute, inflammatory phase of wound healing. From teinases. However, no direct evidence for its function in the kinetics and topology of SKALP expression we vivo is available at present. Previous investigations have surmise that it negatively regulates PMN infiltration.

Skin-derived antileukoproteinase (SKALP), Key words SKALP • Wound healing • also known as elafin, is a proteinase inhibitor with Antileukoproteinase • Elastase specificity for polymorphonuclear leucocyte (PMN)-derived elastase and proteinase-3. SKALP is absent in normal human epidermis, but is strongly induced in Introduction inflammatory dermatoses such as psoriasis. SKALP is putatively involved in the regulation of cutaneous in-Proteinase activity is regulated systemically by numerous flammation by inhibiting PMN derived proteinases. plasma-derived inhibitors, such as a!-proteinase inhibitor The aim of this study was to investigate SKALP ex-and a 2-macroglobulin. However, in normal human epipression and PMN infiltration during wound healing dermis only low levels of antiproteinase activity directed in human skin. This was examined in healing exci-against the major polymorphonuclear leucocyte (PMN)-sional wounds in normal skin and in impaired healing derived proteinases (e.g. elastase, proteinase-3 and cathepin various types of chronic venous ulcers. Tissues were sin G) can be detected. Antiproteinase activity is upreguanalysed using immunohistocliemistry and Northern lated in inflammatory skin diseases such as psoriasis [5, blot analysis. Healing of excisional wounds was stud-18-20] and epidermal tumours [2]. In previous studies we ied from day 0 to day 14. An influx of PMN was seen and others have characterized this antiproteinase activity rapidly after wounding and was maximal between day and found it to be an inducible inhibitor of elastase and 2 and 4 and then subsided. SKALP was induced within proteinase 3 [23]. This inhibitor has been named skin-de-48 h and was expressed in the suprabasal keratino-rived antileukoproteinase (SKALP) [18], also known as cytes of the wound edge and the migrating epidermal elafin [23,24] or elastase-specific inhibitor (ESI) [15 |. sheet. SKALP expression was maximal on day 4 and Cloning of the SKALP cDNA and gene has revealed that was downregulated at the time of complete reepithe-the molecule contains several N-terminal transglutamilialization (7-14 days). In venous ulcers, PMN were nase substrate motifs, in addition to the antiproteinase doabundant in the wound bed and scarce under the main that was already known [11,12,14]. SKALP is a sewound edge. SKALP was strongly expressed in the creted molecule, and we have recently demonstrated its keratinocytes of the wound edge in all types of ulcers presence in urine and plasma of psoriatic patients [1,4]. studied. In the wound bed, SKALP was not detectable. Our results suggest that S SKALP may be involved in the regulation of euta-P plays a role in the neous animation by inhibiting PMN-derived o acute, inflammatory phase of wound healing. From teinases. However, no direct evidence for its function in the kinetics and topology of SKALP expression we vivo is available at present. Previous investigations have surmise that it negatively regulates PMN infiltration.

ZusammenfassungEs wird über einen zehnjährigen Jungen mit einer linearen Rötung über der rechten Augenbraune und einer Rille im unterliegen den Schädelknochen berichtet. SchlüsselwörterLineare Sklerodermie (en coup de sabre) *

In this study we have investigated epidermal growth and differentiation during wound healing in human skin. The studies were performed in excisional wounds in normal skin and in chronic venous ulcers. Tissues were analyzed by immunohistochemical staining for proliferation-associated nuclear antigens (PCNA and Ki-67 antigen) and cytokeratin 16. Healing of excisional wounds was studied from day 2 to 14. Recruitment of resting (G0) epidermal cells started within 2 days after wounding

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