Fas/Fas配体介导的凋亡在固定性药疹发病机制中的可能作用  

Possible role of Fas/Fas ligand-mediated apoptosis in the pathogenesis of fixed drug eruption

作　　者：Choi H.J. Kim M.Y. Y.M. Park 罗素菊 

机构地区：[1]Department of Dermatology, Kangnam St. Mary's Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, South Korea

出　　处：《世界核心医学期刊文摘（皮肤病学分册）》2006年第6期35-35,共1页Digest of the World Core Medical JOurnals:Dermatology

摘　　要：Background: Although epidermal and dermal T cells play roles in the pathogenesis of fixed drug eruption (FDE), not much is known about keratinocyte death and its precise mechanism in FDE. Objectives: Our aim is to elucidate the mechanism that underlies keratinocyte death in FDE, that is, the role of apoptosis and its signalling pathway. Methods: We first examined the involvement of apoptosis in the active FDE lesions by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelli- ng (TUNEL) assay and immunohistochemical analysis of caspase-3. We then examined the expressions of Fas and Fas ligand (FasL) to deduce the possible upstream signalling pathway of apoptosis, if apoptosis were involved. We finally characterized the infiltrated T-cell subpopulations in the active FDE lesions. Results: In the active FDE lesions, TUNEL positivity was strongly observed in the basal keratinocytes, and also weakly observed in the upper dermal infiltrates as well as in a few keratinocytes in the granular layer. The distribution of TUNEL-positive cells was similar to that of the strong staining of active capase-3. Fas was found mainly in the keratinocytes and some infiltrated dermal cells, whereas FasL was identified predominantly in the intraepidermal and dermal infiltrated cells and in some basal keratinocytes. Overlapping expression of Fas and FasL was accompanied by apoptosis in the FDE lesions. Many of the infiltrated mononuclear cells were CD8+. Perforin was rarely observed in the FDE lesions. Conclusions: These findings suggest that apoptosis of the keratinocyte is highly likely to be involved in the pathogenesis of FDE, and this cytotoxicity might be predominantly mediated by the FasL of the infiltrating CD8+T cells, possibly also playing an inflammatory role.Background： Although epidermal and dermal T ceils play roles in the pathogenesis of fixed drug eruption （FDE）, not much is known about keratinocyte death and its precise mechanism in FDE. Objectives： Our aim is to elucidate the mechanism that underlies keratinocyte death in FDE, that is, the role of apoptosis and its signalling pathway. Methods： We first examined the involvement of apoptosis in the active FDE lesions by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling （TUNEL） assay and immunohistochemical analysis of caspase-3. We then examined the expressions of Fas and Fas ligand （FasL） to deduce the possible upstream sig- nalling pathway of apoptosis, if apoptosis were involved. We finally characterized the infiltrated T-cell subpopulations in the active FDE lesions. Results： In the active FDE lesions, TUNEL positivity was strongly observed in the basal keratinocytes, and also weakly observed in the upper dermal infiltrates as well as in a few keratinocytes in the granular layer. The distribution of TUNEL-positive cells was similar to that of the strong staining of active capase-3. Fas was found mainly in the keratinocytes and some infiltrated dermal ceils, whereas FasL was identified predominantly in the intraepidermal and dermal infiltrated cells and in some basal keratinocytes. Overlapping expression of Fas and FasL was accompanied by apoptosis in the FDE lesions. Many of the infiltrated mononuclear cells were CD8＋. Perforin was rarely observed in the FDE lesions. Conclusions： These findings suggest that apoptosis of the keratinocyte is highly likely to be involved in the pathogenesis of FDE, and this cytotoxicity might be predomignantly mediated by the FasL of the infiltrating CD8 ＋ T cells, possibly also playing an inflammatory role.

关 键 词：FAS/FAS配体 固定性药疹 发病机制 酶介导 活性caspase-3 TUNEL阳性细胞 凋亡 角质形成细胞 CD8+T细胞 脱氧核苷酰 

分 类 号：R512.6[医药卫生—内科学] R758.25[医药卫生—临床医学]