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.

Knowledge of the physiology of wound healing, in particular the recovery of the dermal and epidermal compartments and the co-ordination of these processes by the cytokine network, is of great importance to rational wound management. The individual components of the wound healing process have been studied using various in vitro and in vivo models, comparing young, adult and aged individuals. Many of the processes involved in wound healing are impaired in the elderly. However, in elderly patients not suffering from concomitant diseases, the rate of wound healing is normal or only slightly reduced. Various 'systemic factors' (endocrine and haematological diseases, nutritional deficiencies and medications) and 'regional disorders' (vascular and neural diseases) may impair wound healing. These complicating conditions occur more frequently in aged subjects. Failure of wound healing in the elderly is a chronic disabling condition, which occurs frequently in our society, requiring a major investment of medical care.