Matrix metalloproteinases and tissue inhibitors of metalloproteinases in viral meningitis: upregulation of MMP-9 and TIMP-1 in cerebrospinal fluid
Matrix metalloproteinases and tissue inhibitors of metalloproteinases in viral meningitis: upregulation of MMP-9 and TIMP-1 in cerebrospinal fluid
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DOI：
10.1016/s0165-5728(97)00247-6
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发表时间：
1998-04-15
影响因子：
3.3
通讯作者：
Fontana, A
中科院分区：
文献类型：
--
作者：
Kolb, SA;Lahrtz, F;Fontana, A
病毒性脑膜炎的一个标志是单核细胞、淋巴细胞以及在疾病的初始阶段中性粒细胞侵入蛛网膜下腔。通过降解细胞外结缔组织中的不同大分子成分，基质金属蛋白酶（MMP）可能对于脑膜和脉络丛血管壁的破坏至关重要。在这项研究中，监测了病毒性脑膜炎患者脑脊液 (CSF) 中 MMP-1、MMP-2、MMP-3 和 MMP-9 以及两种金属蛋白酶组织抑制剂 TIMP-1 和 TIMP-2 的出现情况。在这些蛋白酶中，39 名患者中有 13 名 (33%) 发现了 MMP-9，但在对照组中未发现；该水平与脑脊液中的中性粒细胞数量相关。与对照组相比，CSF 中 TIMP-1 浓度增加了三倍（中位数 233 ng/ml；范围 9.4-1252.5 ng/ml），并且与 CSF 中总蛋白水平相关。在检测的其他 MMP 和 TIMP 中，MMP-2 和 TIMP-2 在病毒性脑膜炎中持续表达且未上调。通过 ELISA 测量，高水平的 MMP-9 和 MMP-2 与通过酶谱法在 CSF 中检测到的高蛋白水解活性相关。总之，病毒性脑膜炎中白细胞侵入脑脊液可能涉及 MMP-9，其蛋白水解作用可能受 TIMP-1 表达控制。 (C) 1998 Elsevier Science B.V.
A hallmark of viral meningitis is the invasion of monocytes, lymphocytes and, in the initial phase of the disease, neutrophils into the subarachnoidal space. By their degradation of different macromolecular components in the extracellular connective tissue, matrix metalloproteinases (MMPs) may be essential for the breakdown of the vessel wall in the meninges and the choroid plexus. In this study, the occurrence of MMP-1, MMP-2, MMP-3 and MMP-9 and the two tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, was monitored in the cerebrospinal fluid (CSF) from patients with viral meningitis. Of the proteinases, MMP-9 was found in 13 of 39 (33%) patients, but not in controls; the levels being correlated with the neutrophil cell number in CSF. The CSF concentration of TIMP-1 was increased three-fold compared to the control group (median 233 ng/ml; range 9.4-1252.5 ng/ml) and was correlated to the levels of total protein in CSF. Of the other MMPs and TIMPs assayed, MMP-2 and TIMP-2 were constitutively expressed and not upregulated in viral meningitis. High levels of MMP-9 and MMP-2, as measured by ELISA, was associated with high proteolytic activity detected in CSF by zymography. In conclusion, invasion of the leukocytes into the CSF compartment in viral meningitis may involve MMP-9, its proteolytic effect likely being controlled by expression of TIMP-1. (C) 1998 Elsevier Science B.V.