Kolb S A, Lahrtz F, Paul R, Leppert D, Nadal D, Pfister H W, Fontana A
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
J Neuroimmunol. 1998 Apr 15;84(2):143-50. doi: 10.1016/s0165-5728(97)00247-6.
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.
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初始阶段中性粒细胞侵入蛛网膜下腔。基质金属蛋白酶（MMPs）通过降解细胞外结缔组织中的不同大分子成分，可能在脑膜和脉络丛血管壁的破坏中起关键作用。在本研究中，对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的出现情况进行了监测。在蛋白酶中，39例患者中有13例（33%）检测到MMP - 9，而对照组未检测到；其水平与CSF中的中性粒细胞数量相关。与对照组相比，TIMP - 1的CSF浓度增加了两倍（中位数为233 ng/ml；范围为9.4 - 1252.5 ng/ml），并且与CSF中的总蛋白水平相关。在检测的其他MMPs和TIMPs中，MMP - 2和TIMP - 2组成性表达，在病毒性脑膜炎中未上调。通过酶联免疫吸附测定法（ELISA）测量的高水平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CSF腔室可能涉及MMP - 9，其蛋白水解作用可能受TIMP - 1表达的控制。
