The significance of matrix metalloproteinases in parasitic infections involving the central nervous system.
The significance of matrix metalloproteinases in parasitic infections involving the central nervous system.
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DOI：
10.3390/pathogens2010105
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发表时间：
2013-02-19
期刊：
影响因子：
--
通讯作者：
Pinto B
中科院分区：
文献类型：
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作者：
Bruschi F;Pinto B
基质金属蛋白酶（MMPs）代表超过20种不同分泌或膜结合内肽酶的大家族，其参与许多生理（胚胎发生、前体细胞或干细胞动员、伤口愈合期间的组织重塑等），以及病理学（炎症、肿瘤进展和癌症转移、血管病理学等）条件长期以来，MMPs仅被认为具有降解细胞外基质（ECM）分子（例如，胶原蛋白、层粘连蛋白、纤连蛋白）并从ECM释放隐藏的表位。在过去的几年中，考虑到它们对细胞因子、激素和趋化因子的作用，已经充分阐明了这些分子具有许多其他功能，主要与免疫应答相关。其中，MMP-2和MMP-9是由嗜中性粒细胞、巨噬细胞和单核细胞产生的MMP家族的内肽酶。当感染与白细胞流入特定器官相关时，可能发生免疫病理学和附带组织损伤。在这篇评论中，基质金属蛋白酶的参与，特别是明胶酶在原生动物和蠕虫感染将被描述。例如，在脑型疟疾中，MMPs在这类疾病的发病机制中发挥作用。此外，锥虫病和弓形虫病将被认为是原生动物感染，以及神经囊虫病和管圆线虫病，就蠕虫病而言。所有这些情况都有一个共同点，即由MMPs介导的对血脑屏障的蛋白水解作用。
Matrix metalloproteinases (MMPs) represent a large family of over twenty different secreted or membrane-bound endopeptidases, involved in many physiological (embryogenesis, precursor or stem cell mobilization, tissue remodeling during wound healing, etc.), as well as pathological (inflammation, tumor progression and metastasis in cancer, vascular pathology, etc.) conditions. For a long time, MMPs were considered only for the ability to degrade extracellular matrix (ECM) molecules (e.g., collagen, laminin, fibronectin) and to release hidden epitopes from the ECM. In the last few years, it has been fully elucidated that these molecules have many other functions, mainly related to the immune response, in consideration of their effects on cytokines, hormones and chemokines. Among others, MMP-2 and MMP-9 are endopeptidases of the MMP family produced by neutrophils, macrophages and monocytes. When infection is associated with leukocyte influx into specific organs, immunopathology and collateral tissue damage may occur. In this review, the involvement of MMPs and, in particular, of gelatinases in both protozoan and helminth infections will be described. In cerebral malaria, for example, MMPs play a role in the pathogenesis of such diseases. Also, trypanosomosis and toxoplasmosis will be considered for protozoan infections, as well as neurocysticercosis and angiostrongyloidosis, as regards helminthiases. All these situations have in common the proteolytic action on the blood brain barrier, mediated by MMPs.