The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: Comparison of stages in lesion evolution
The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: Comparison of stages in lesion evolution
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DOI：
10.1097/00005072-199612000-00002
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发表时间：
1996-12-01
影响因子：
3.2
通讯作者：
Newcombe, J
中科院分区：
文献类型：
--
作者：
Cuzner, ML;Gveric, D;Newcombe, J
采用免疫组织病理学方法分析了正常对照和多发性硬化症（MS）患者中枢神经系统（CNS）组织型纤溶酶原激活物（t-PA）、多种金属蛋白酶以及纤溶酶原激活物抑制剂-1 （PAI-1）和金属蛋白酶组织抑制剂-1 （TIMP-1）的表达。t-PA仅在对照白质的血管基质中表达，但在MS白质和原发病变中也可见浸润性单核细胞阳性。在活动性斑块中，这种模式在脱髓鞘区域转化为泡沫巨噬细胞的强阳性，在慢性病变中下降。PAI-1表达与t-PA表达一致。明胶酶A和B主要在正常对照白质的星形胶质细胞和小胶质细胞中检测到，在MS白质的血管周围袖带中也有阳性的单核细胞。在脱髓鞘病变中，明胶酶B在反应性星形胶质细胞和巨噬细胞中广泛表达，在慢性病变的星形胶质细胞中持续表达。TIMP-1也存在于血管基质和病变巨噬细胞中。这些对CNS组织中基质降解级联酶和抑制剂的共表达的观察表明，t-PA（一种限速酶）和明胶酶B是多发性硬化症的治疗靶点。
The expression of tissue-type plasminogen activator (t-PA) and a number of metalloproteases as well as plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteases-1 (TIMP-1) was analyzed in the central nervous system (CNS) of normal control and multiple sclerosis (MS) cases by immunohistopathology. The expression of t-PA was detectable only in the blood vessel matrix in control white matter, but positive infiltrating mononuclear cells were also observed in MS white matter and primary lesions. In active plaques this pattern converted to strong positivity of foamy macrophages in areas of demyelination, declining in chronic lesions. In general PAI-1 expression paralleled that of t-PA. Gelatinase A and B were detected predominantly in astrocytes and microglia throughout normal control white matter, with additional positive mononuclear cells in perivascular cuffs in MS white matter. In the demyelinating lesion there is widespread prominent expression of gelatinase B in reactive astrocytes and macrophages, which persists in astrocytes in the chronic lesion. TIMP-1 was also present in the vessel matrix and in lesional macrophages. These observations on the coexpression of enzymes and inhibitors of the matrix degrading cascade in CNS tissue pinpoint t-PA, a rate-limiting enzyme, and gelatinase B as therapeutic targets in MS.