Chapter category: Infectious Disease

Activation of BradykininReceptors by Trypanosoma cruzi: A Role for Cruzipain in Microvascular Pathology

This chapter appears in the following book:

Molecular Mechanisms of Pathogenesis in Chagas Disease

Edited by: JohnM. Kelly
ISBN: 0-306-47849-8
» Get more information about this book at landesbioscience.com «

Chapter authors:
Julio Scharfstein

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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⁺]_itransients 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.

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Chapter category: Infectious Disease

Activation of BradykininReceptors by Trypanosoma cruzi: A Role for Cruzipain in Microvascular Pathology

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