Gaultier F, Ejeil A-L, Igondjo-Tchen S, Dohan D, Dridi S M, Maman L, Wierzba C B, Stania D, Pellat B, Lafont A, Godeau G, Gogly B
Laboratory of Physiopathology of Non-mineralized Tissues, University René Descartes PARIS V, U. F. R. Odontology, 1 rue M. Arnoux, 92120 Montrouge, France.
Arch Dermatol Res. 2004 Oct;296(5):220-5. doi: 10.1007/s00403-004-0506-z. Epub 2004 Sep 22.
Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are considered to be drug-induced diseases, and are characterized by extensive mucocutaneous disorder and epidermal necrosis which result in the detachment of the epidermis. Inactive and active forms of metalloproteinases (MMP2 and MMP9) secreted by skin explants maintained in organ culture for 72 h and in blister fluid from two TEN and three SJS patients were investigated. Interestingly, lesional skin from both the TEN and the SJS patients cultured for 3 days in conditioned medium showed high levels of both 72 kDa progelatinase A and 66 kDa activated gelatinase A, and the 66 kDa activated form was not observed in cultures of skin from control individuals. Furthermore, indirect immunodetection showed the presence of MMP2 and MMP9 in TEN and SJS patients' skin. Increased gelatinase activity in the culture medium of TEN and SJS skin maintained in organ culture and in blister fluid indicates that these gelatinases may be responsible for the detachment of the epidermis in these drug-induced necrolyses.
中毒性表皮坏死松解症(TEN)和史蒂文斯-约翰逊综合征(SJS)被认为是药物诱导性疾病,其特征为广泛的黏膜皮肤病变和表皮坏死,进而导致表皮脱落。对在器官培养中维持72小时的皮肤外植体以及两名TEN患者和三名SJS患者的水疱液中分泌的金属蛋白酶(MMP2和MMP9)的非活性和活性形式进行了研究。有趣的是,在条件培养基中培养3天的TEN和SJS患者的病变皮肤均显示出高水平的72 kDa前明胶酶A和66 kDa活性明胶酶A,而在对照个体皮肤培养物中未观察到66 kDa活性形式。此外,间接免疫检测显示TEN和SJS患者皮肤中存在MMP2和MMP9。在器官培养中维持的TEN和SJS皮肤培养基以及水疱液中明胶酶活性增加,表明这些明胶酶可能是这些药物诱导的坏死松解症中表皮脱落的原因。