%0 Journal Article
%T Matrix Metalloproteinase-9 and Haemozoin: Wedding Rings for Human Host and Plasmodium falciparum Parasite in Complicated Malaria
%A Mauro Prato
%A Giuliana Giribaldi
%J Journal of Tropical Medicine
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/628435
%X 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. 1. Introduction Among protozoan parasites of the genus Plasmodium, P. falciparum is the most deadly agent of human malaria, causing a broad spectrum of clinical manifestations ranging from asymptomatic to severe multiorgan disease. Despite recent major efforts by the research community, malaria remains one of the major diseases in poor areas, including Sub-Saharan Africa and South-East Asia. It is associated with several million clinical cases per year and leads annually to over one million deaths [1, 2]. The pathophysiology of severe malaria complications is not well understood. In some cases, including cerebral malaria (CM), renal failure, lung pathology and malaria during pregnancy, it appears associated with cytoadherence and sequestration of P. falciparum-parasitized red blood cells (pRBCs) to vascular endothelium, leading to microcirculatory obstruction, tissue hypoxia, and metabolic disturbances [3¨C5]. In some cases additional leukocyte extravasation has been reported [6, 7]. As described in the following sections, either pRBCs or parasite products such as haemozoin (HZ, malarial pigment), a lipid-enriched ferriprotoporphyrin IX crystal derived from haemoglobin catabolism by the parasite [8], can modulate the functions of mononuclear and endothelial cells and promote the production of proinflammatory molecules and other soluble factors, including matrix metalloproteinases (MMPs). MMPs are a well-known family of proteolytic enzymes able to disrupt subendothelial basement membranes [9, 10], to destroy tight junctions [11], and to shed, activate, or inactivate
%U http://www.hindawi.com/journals/jtm/2011/628435/