Plumb J, McQuaid S, Cross A K, Surr J, Haddock G, Bunning R A D, Woodroofe M N
Biomedical Research Centre, Sheffield Hallam University, Howard St, Sheffield S1 1WB, UK.
Mult Scler. 2006 Aug;12(4):375-85. doi: 10.1191/135248506ms1276oa.
ADAM-17, a disintegrin and metalloproteinase, is the major proteinase responsible for the cleavage of membrane-bound tumour necrosis factor (TNF) as well as being an active sheddase of other cytokines, cytokine receptors, growth factors and adhesion molecules. TNF is a major proinflammatory cytokine that has been identified as having a pathogenic role in inflammatory diseases within the CNS including multiple sclerosis (MS). Here we report the cellular origin and distribution of ADAM-17 expression within clinically and neuropathologically confirmed MS and normal control white matter, assessed by immunohistochemistry, western blotting and PCR. ADAM-17 expression was associated with the blood vessel endothelium, activated macrophages/microglia and parenchymal astrocytes in MS white matter. Increased levels of ADAM-17 immunoreactivity were displayed in active lesions with evidence of recent myelin breakdown. Further studies into the functional role of ADAM-17 in the pathogenesis of MS and other inflammatory conditions are required.
ADAM-17是一种去整合素和金属蛋白酶，是负责切割膜结合肿瘤坏死因子（TNF）的主要蛋白酶，也是其他细胞因子、细胞因子受体、生长因子和黏附分子的活性脱落酶。TNF是一种主要的促炎细胞因子，已被确定在包括多发性硬化症（MS）在内的中枢神经系统炎症性疾病中具有致病作用。在此，我们通过免疫组织化学、蛋白质印迹法和聚合酶链反应，报告了临床和神经病理学确诊的MS以及正常对照白质中ADAM-17表达的细胞起源和分布。ADAM-17表达与MS白质中的血管内皮、活化的巨噬细胞/小胶质细胞和实质星形胶质细胞相关。在有近期髓鞘破坏证据的活动性病变中，ADAM-17免疫反应性水平升高。需要进一步研究ADAM-17在MS和其他炎症性疾病发病机制中的功能作用。
