Chen Ke-Min, Liu Jer-Yuh, Lai Shih-Chan, Hsu Li-Sung, Lee Hsiu-Hsiung
Department of Parasitology, Chung Shan Medical University, Taichung 402, Taiwan.
Int J Exp Pathol. 2006 Apr;87(2):113-9. doi: 10.1111/j.0959-9673.2006.00459.x.
Blood-central nervous system (blood-CNS) barrier breakdown, an important pathophysiological event in meningitis, results in extravasation of leucocytes into subarachnoid space. The blood-CNS barrier disruption is mediated by primarily two enzyme systems, the plasminogen activators (PAs) and matrix metalloproteinases (MMPs). The present study showed that the activities of tissue-type PA (tPA), urokinase-type activator (uPA) and MMP-9 in cerebrospinal-like fluid (CSF-like fluid) were significantly increased in mice with eosinophilic meningitis compared with uninfected mice. Eosinophilia significantly correlated with tPA, uPA and MMP-9 activities, and albumin concentration. In addition, when GM6001, a specific matrix metalloproteinase blocker, was injected into infected mice, MMP-9 activity and total protein concentrations declined from their preinjection highs. These results suggest that the PAs and MMP-9 proteolytic cascade may be associated with blood-CNS barrier disruption in eosinophilic meningitis caused by Angiostrongylus cantonensis.
血脑屏障破坏是脑膜炎中的一个重要病理生理事件，可导致白细胞渗入蛛网膜下腔。血脑屏障破坏主要由两种酶系统介导，即纤溶酶原激活剂（PAs）和基质金属蛋白酶（MMPs）。本研究表明，与未感染小鼠相比，嗜酸性粒细胞性脑膜炎小鼠脑脊液样液中组织型PA（tPA）、尿激酶型激活剂（uPA）和MMP-9的活性显著增加。嗜酸性粒细胞增多与tPA、uPA和MMP-9活性以及白蛋白浓度显著相关。此外，当向感染小鼠注射特异性基质金属蛋白酶阻滞剂GM6001时，MMP-9活性和总蛋白浓度从注射前的高水平下降。这些结果表明，PAs和MMP-9蛋白水解级联反应可能与广州管圆线虫引起的嗜酸性粒细胞性脑膜炎中的血脑屏障破坏有关。
