1. Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis
- Author
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You-Di Liao, Chih-Hsun Yang, Chien-Chun Chiou, Shien-Ping Huang, Chun-Yu Wei, See-Wen Chin, Yuan-Tsong Chen, Hsin-Chun Ho, Jer-Yuarn Wu, Jui-Yung Yang, Shih-Chi Su, Wen-Hung Chung, Chi-Fang Lu, Sung-Chao Chu, and Shuen-Iu Hung
- Subjects
Antigens, Differentiation, T-Lymphocyte ,Keratinocytes ,Biopsy ,Mice, Nude ,General Biochemistry, Genetics and Molecular Biology ,Mice ,Necrosis ,Blister ,GNLY ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Granulysin ,Cytotoxicity ,integumentary system ,biology ,Gene Expression Profiling ,General Medicine ,medicine.disease ,Toxic epidermal necrolysis ,Killer Cells, Natural ,Molecular Weight ,Granzyme B ,stomatognathic diseases ,medicine.anatomical_structure ,Epidermal Cells ,Gene Expression Regulation ,Perforin ,Stevens-Johnson Syndrome ,Immunology ,biology.protein ,Epidermis ,Keratinocyte ,T-Lymphocytes, Cytotoxic - Abstract
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse drug reactions characterized by massive epidermal necrosis, in which the specific danger signals involved remain unclear. Here we show that blister cells from skin lesions of SJS-TEN primarily consist of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and both blister fluids and cells were cytotoxic. Gene expression profiling identified granulysin as the most highly expressed cytotoxic molecule, confirmed by quantitative PCR and immunohistochemistry. Granulysin concentrations in the blister fluids were two to four orders of magnitude higher than perforin, granzyme B or soluble Fas ligand concentrations, and depleting granulysin reduced the cytotoxicity. Granulysin in the blister fluids was a 15-kDa secretory form, and injection of it into mouse skin resulted in features mimicking SJS-TEN. Our findings demonstrate that secretory granulysin is a key molecule responsible for the disseminated keratinocyte death in SJS-TEN and highlight a mechanism for CTL- or NK cell—mediated cytotoxicity that does not require direct cellular contact. Adverse drug reactions (ADRs) account for 6–7% of all hospital admissions and remain a major clinical problem 1 . Among them, SJS
- Published
- 2008