Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke
Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke
复制标题
DOI：
10.1111/j.1365-2990.1997.tb01315.x
复制
发表时间：
1997-10-01
影响因子：
5
通讯作者：
Perry, VH
中科院分区：
文献类型：
--
作者：
Anthony, DC;Ferguson, B;Perry, VH
多发性硬化症（MS）和中风的病理特征是血脑屏障破坏，白细胞迁移和组织破坏。每个过程都被认为涉及基质金属蛋白酶（MMP），但对它们的表达知之甚少。我们开始研究MMP的表达是否依赖于中枢神经系统病变的性质，以及表达是否与组织病理学一致。检测MS或脑梗死组织中明胶酶a、明胶酶b、基质溶素和基质溶素-1的存在。明胶酶A、B和基质溶素在急性MS病变的小胶质细胞/巨噬细胞中表达上调。在活动的慢性MS病变中，基质溶素和明胶酶- a在活动边界明显表达。在慢性MS病变中，基质溶素的表达仅限于血管周围的巨噬细胞。MMP在梗死灶中的表达模式差异较大。明胶酶- b在梗死后1周内由患者组织中的中性粒细胞强烈表达，而明胶酶-a和基质溶素染色则不那么明显。从1周到5年，中性粒细胞缺失，大量巨噬细胞表达母溶酶和明胶酶a。在正常脑对照中，只有低水平的明胶酶a和明胶酶a表达。因此，MMPs在中枢神经系统的炎性病变中表达，但其个体表达取决于病变的性质和慢性性。然而，在血管周围袖带和活动性病变中的一般表达模式支持这些酶在MS和脑缺血中作为血脑屏障破坏和组织破坏的介质的作用。
Multiple sclerosis (MS) and stroke pathology are characterized by blood-brain barrier breakdown, leucocyte emigration, and tissue destruction. Each process is thought to involve the matrix metalloproteinases (MMP), but little is known of their expression. We undertook to investigate whether MMP expression is dependent on the nature of the CNS lesion and whether expression would coincide with the histopathology. MS or cerebral-infarct tissue was examined for the presence of gelatinase-A, gelatinase-B, matrilysin and stromelysin-1. Gelatinases A and B and matrilysin expression was found to be up-regulated in microglia/macrophages within acute MS lesions. In active-chronic MS lesions, matrilysin and gelatinase-A expression was pronounced in the active borders. In chronic MS lesions, the expression of matrilysin was confined to macrophages within perivascular cuffs. The pattern of MMP expression in infarct lesions differed considerably. Gelatinase-B was strongly expressed by neutrophils in tissue from patients up to 1 week after an infarct, whereas gelatinase-a and matrilysin staining was much less marked. From 1 week to 5 years, neutrophils were absent and the large number of macrophages present were expressing matrilysin and gelatinase A. Only a low level of gelatinase-A and matrilysin expression was observed in normal brain controls. Thus, MMPs are expressed in inflammatory lesions in the CNS, but their individual expression is dependent on the nature and chronicity of the lesion. However, the general pattern of expression, in perivascular cuffs and in active lesions, supports a role for these enzymes as mediators of blood-brain barrier breakdown and tissue destruction, both in MS and in cerebral ischaemia.