SKIN-DERIVED ANTILEUKOPROTEINASE (SKALP) IS DECREASED IN PUSTULAR FORMS OF PSORIASIS - A CLUE TO THE PATHOGENESIS OF PUSTULE FORMATION

Skin-derived antileukoproteinase (SKALP, also known as elafin) is an i nducible epidermal serine proteinase inhibitor, that we have recently characterized at the protein and DNA levels, SKALP is a strong and spe cific inhibitor of PMN elastase, and is putatively involved in the reg ulation of cutaneous inflammatory processes, In order to investigate t he role of SKALP in the control of elastase in psoriatic epidermis, we compared SKALP expression in normal skin, and in skin from patients w ith chronic plaque psoriasis and pustular forms of psoriasis, Epiderma l scales and biopsies were collected and SKALP expression was studied at the mRNA level and at the protein level both functionally and immun ochemically. In epidermal scales, we found that the levels of both fre e and total SKALP activity in pustular psoriasis were far lower than i n plaque psoriasis. A significant number of pustular psoriasis patient s showed latent SKALP activity, which represents the amount of SKALP p utatively complexed to elastase, In addition, we found free elastase a ctivity in 25% of the pustular psoriasis patients, indicating a total saturation of epidermal SKALP activity, In epidermal biopsies from pus tular psoriasis patients, SKALP activity was significantly decreased c ompared with those from plaque psoriasis patients, Northern blot analy sis did not reveal differences in epidermal mRNA levels between chroni c plaque psoriasis and pustular psoriasis. We hypothesize that a reduc ed amount of epidermal SKALP contributes to an imbalance between elast ase and its inhibitor, thereby promoting the formation of epidermal pu stules, We suggest that these findings could provide a rationale for t he treatment of pustular psoriasis with inhibitors of PMN-derived prot einases, as a new therapeutic modality.