Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by soluble Fas ligand

Toxic epidermal necrolysis and Stevens-Johnson syndrome are induced by soluble Fas ligand
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DOI:
10.1016/s0002-9440(10)64284-8
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发表时间:
2003-05-01
影响因子:
6
通讯作者:
Shimizu, H
Shimizu, H
中科院分区:
医学2区
文献类型:
--
作者:
Abe, R;Shimizu, T;Shimizu, H

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中毒性表皮坏死松解症(TEN)和史蒂文斯约翰逊综合征(SJS)这两种严重的水疱性疾病通常与药物摄入有关,其发病机制尚未完全阐明。在组织学上,TEN 和 SJS 的特征都是广泛的角质形成细胞凋亡。先前的研究表明,TEN 和 SJS 中的角质形成细胞凋亡是由 Fas 和 Fas 配体 (FastL) 之间的自杀性相互作用诱导的,Fas 和 Fas 配体 (FastL) 均由角质形成细胞表达。然而,我们的初步检查表明,在角质形成细胞上几乎检测不到FasL。我们假设可溶性 FasL (sFasL) 由外周血单核细胞 (PBMC) 分泌,并且与 TEN 和 SJS 中角质形成细胞上表达的 Fas 相互作用。为了证明这一假设,我们研究了 PBMC 分泌的 sFasL 是否可以诱导 TEN 和 SJS 中的角质形成细胞凋亡。酶联免疫吸附测定分析表明,健康对照的任何样本中 sFasL 均没有显着增加(
The pathogeneses of toxic epidermal necrolysis (TEN) and Stevens Johnson syndrome (SJS), both severe blistering diseases usually associated with drug intake, are not fully elucidated. Histologically, both TEN and SJS are characterized by extensive keratinocyte apoptosis. Previous studies have shown that keratinocyte apoptosis in TEN and SJS was induced by a suicidal interaction between Fas and Fas ligand (FastL), which are both expressed by keratinocytes. However, our preliminary examinations demonstrated that FasL is hardly detected on keratinocytes. We hypothesized that soluble FasL (sFasL) is secreted by peripheral blood mononuclear cells (PBMCs), and this interacts with the Fas expressed on keratinocytes in TEN and SJS. To justify this hypothesis, we investigated whether sFasL secreted by PBMCs could induce the keratinocyte apoptosis in TEN and SJS. Enzyme-linked immunosorbent assay analysis demonstrated that there was no significant sFasL increase in any samples of healthy controls (