Kuijpers A L, Zeeuwen P L, de Jongh G J, van de Kerkhof P C, Alkemade H A, Schalkwijk J
Department of Dermatology, University Hospital Nijmegen, The Netherlands.
Arch Dermatol Res. 1996 Oct;288(11):641-7. doi: 10.1007/BF02505272.
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.
皮肤衍生抗白细胞蛋白酶（SKALP，也称为弹性蛋白酶抑制因子）是一种可诱导的表皮丝氨酸蛋白酶抑制剂，我们最近在蛋白质和DNA水平对其进行了表征。SKALP是中性粒细胞弹性蛋白酶的强效特异性抑制剂，可能参与皮肤炎症过程的调节。为了研究SKALP在银屑病表皮弹性蛋白酶控制中的作用，我们比较了正常皮肤、慢性斑块状银屑病患者皮肤和脓疱型银屑病患者皮肤中SKALP的表达。收集表皮鳞屑和活检组织，从mRNA水平以及功能和免疫化学方面的蛋白质水平研究SKALP的表达。在表皮鳞屑中，我们发现脓疱型银屑病中游离和总SKALP活性水平均远低于斑块状银屑病。大量脓疱型银屑病患者表现出潜在的SKALP活性，这代表了假定与弹性蛋白酶复合的SKALP量。此外，我们在25%的脓疱型银屑病患者中发现了游离弹性蛋白酶活性，表明表皮SKALP活性完全饱和。与斑块状银屑病患者的表皮活检组织相比，脓疱型银屑病患者的表皮活检组织中SKALP活性显著降低。Northern印迹分析未揭示慢性斑块状银屑病和脓疱型银屑病之间表皮mRNA水平的差异。我们推测表皮SKALP量的减少导致弹性蛋白酶与其抑制剂之间的失衡，从而促进表皮脓疱的形成。我们认为这些发现可为使用中性粒细胞衍生蛋白酶抑制剂治疗脓疱型银屑病提供理论依据，作为一种新的治疗方式。
