Dipartimento di Genetica, Biologia e Biochimica, Facoltà di Medicina e Chirurgia, Università di Torino, Via Santena 5 bis, 10126 Torino, Italy.
J Trop Med. 2011;2011:628435. doi: 10.1155/2011/628435. Epub 2011 May 26.
It is generally accepted that the combination of both Plasmodium falciparum parasite and human host factors is involved in the pathogenesis of complicated severe malaria, including cerebral malaria (CM). Among parasite products, the malarial pigment haemozoin (HZ) has been shown to impair the functions of mononuclear and endothelial cells. Different CM models were associated with enhanced levels of matrix metalloproteinases (MMPs), a family of proteolytic enzymes able to disrupt subendothelial basement membrane and tight junctions and shed, activate, or inactivate cytokines, chemokines, and other MMPs through cleavage from their precursors. Among MMPs, a good candidate for targeted therapy might be MMP-9, whose mRNA and protein expression enhancement as well as direct proenzyme activation by HZ have been recently investigated in a series of studies by our group and others. In the present paper the role of HZ and MMP-9 in complicated malaria, as well as their interactions, will be discussed.
一般认为，恶性疟原虫寄生虫和人体宿主因素的结合参与了复杂的严重疟疾的发病机制，包括脑型疟疾（CM）。在寄生虫产物中，疟色素血褐素（HZ）已被证明会损害单核细胞和内皮细胞的功能。不同的 CM 模型与基质金属蛋白酶（MMPs）水平的升高有关，MMPs 是一类能够破坏内皮基底膜和紧密连接的蛋白水解酶，并通过从其前体中切割来释放、激活或失活细胞因子、趋化因子和其他 MMPs。在 MMPs 中，MMP-9 可能是一个有针对性治疗的候选者，因为我们小组和其他小组的一系列研究最近调查了 HZ 对其 mRNA 和蛋白表达的增强以及对其前体的直接酶原激活作用。本文将讨论 HZ 和 MMP-9 在复杂疟疾中的作用及其相互作用。
