Chapter category: Infectious Disease
Activation of BradykininReceptors by Trypanosoma cruzi: A Role for Cruzipain in Microvascular Pathology
Molecular Mechanisms of Pathogenesis in Chagas Disease
Edited by: JohnM. KellyISBN: 0-306-47849-8
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Chapter authors:
Julio Scharfstein
During its life cycle in the mammalian host, Trypanosoma cruzi productively exploits the enzymatic diversity of its own proteases to generate activation signals for a broad range of host cells. At least for the host responses relayed by the G-protein coupled receptors, the generation of the signalling agonists depends on the processing of different inactive precursor molecules by unique parasite proteases. For example, the major cysteine proteinase of T. cruzi, cruzipain, is able to process kininogen molecules that are docked to heparan sulphate proteoglycans, thereby promoting release of vasoactive "kinin" peptides. Whether transduced by constitutive (B2) or inducible (B1) kinin-receptor subtypes, the vigorous [Ca2+]i transients triggered by the shortlived kinin peptides drastically increase host cell susceptibility to trypomastigote invasion. Given the evidence that kinins are rapidly metabolised by host peptidases (e.g., kininase I and II), differences in the tissue levels of these kinin degrading enzymes may influence the extent of organ involvement and pathological outcome in individual patients. Furthermore, recent studies indicate that the kininactivating phenotype is not ubiquitously expressed in the genetically diverse T. cruzi species. Analysis of the mechanisms underlying the kinin releasing activity of parasite strains/clones have tentatively linked this competence to the expression of particular subsets of cruzipain isoforms. Insight on the regulatory checkpoints involved in the activation of the vascular endothelium by T. cruzi may shed light on the pathogenesis of Chagas' disease.
Additional chapters from this book:
How Does Trypanosoma cruzi Survive the Toxic Effects of Reactive Oxygen Species?
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Biological molecules are subject to attack by reactive oxygen species (ROS) leading to membrane disruption, inactivation of essential enzymes, mutagenesis and damage to DNA repair machinery. I...
Activation of BradykininReceptors by Trypanosoma cruzi: A Role for Cruzipain in Microvascular Pathology
Julio Scharfstein
During its life cycle in the mammalian host, Trypanosoma cruzi productively exploits the enzymatic diversity of its own proteases to generate activation signals for a broad range...
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Impact of Polyclonal Lymphocyte Responses on Parasite Evasion and Persistence
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In the field of immunoparasitology it is generally accepted that the survival and degree of pathogenicity of parasites is inextricably linked to their ability to escape and resi...
Ca2+ Signaling in the Invasion of Mammalian Cells by Trypanosoma cruzi
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In order to replicate in the mammalian host, Trypanosoma cruzi must invade host cells. Changes in the intracellular Ca2+ concentration ([Ca2+]i
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The cell surface of Trypanosoma cruzi, the agent of the Chagas disease, is covered by a family of highly O-glycosylated mucin-like glycoproteins. This coat protects the para...
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Genetic Diversity of Trypanosoma cruzi and the Epidemiology of Chagas Disease
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The complex epidemiology of Chagas disease is not fully understood. It has been suggested that distinct genotypes of Trypanosoma cruzi may cause the severe (megasyndromes) and b...
The Role of Nitric Oxide in the Pathogenesis of Trypanosoma cruzi Infection
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This Chapter summarizes the roles of nitric oxide (NO) in mediating and controlling the effector immune response against Trypanosoma cruzi and in the pathology resulting from the infect...
