title: Increased myeloperoxidase activity and protein nitration are indicators of inflammation in patients with Chagas' disease.
abstract: In this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with Chagas' disease. We used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and STAT-PAK immunochromatography) to screen human serum samples (n = 1,481) originating from Chiapas, Mexico, for Trypanosoma cruzi-specific antibodies. We identified 121 subjects who were seropositive for T. cruzi-specific antibodies, a finding indicative of an 8.5% seroprevalence in the rural population from Chiapas. Seropositive and seronegative subjects were examined for plasma levels of biomarkers of inflammation, i.e., myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and xanthine oxidase (XOD), as well as for oxidative (advanced oxidation protein products [AOPPs]) and nitrosative (3-nitrotyrosine [3NT]) biomarkers. The seropositive subjects exhibited a significant increase in MPO activity and protein level, the indicator of neutrophil activation. Subsequently, a corresponding increase in AOPP contents, formed by MPO-dependent hypochlorous acid and chloramine formation, was noted in seropositive subjects. The plasma level of 3NT was significantly increased in seropositive subjects, yet we observed no change in XOD activity (O(2)(-) source) and nitrate/nitrite contents (denotes iNOS activation and NO production), which implied that direct peroxynitrite formation does not contribute to increased nitrosative damage in chagasic subjects. Instead, a positive correlation between increased MPO activity and protein 3NT formation was observed, which suggested to us that MPO-dependent formation of nitrylchloride that occurs in the presence of physiological NO and O(2)(-) concentrations contributes to protein nitration. Overall, our data demonstrate that T. cruzi-induced neutrophil activation is pathological and contributes to MPO-mediated collateral protein oxidative and nitrosative damage in human patients with Chagas' disease. Therapies capable of suppressing MPO activity may be useful in controlling the inflammation and oxidative/nitrosative pathology in chagasic cardiomyopathy.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1070, USA.
authors.forename: Monisha
authors.initials: M
authors.lastname: Dhiman
authors.forename: Jose Guillermo
authors.initials: JG
authors.lastname: Estrada-Franco
authors.forename: Jasmine M
authors.initials: JM
authors.lastname: Pando
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ramirez-Aguilar
authors.forename: Heidi
authors.initials: H
authors.lastname: Spratt
authors.forename: Sara
authors.initials: S
authors.lastname: Vazquez-Corzo
authors.forename: Gladys
authors.initials: G
authors.lastname: Perez-Molina
authors.forename: Rosa
authors.initials: R
authors.lastname: Gallegos-Sandoval
authors.forename: Roberto
authors.initials: R
authors.lastname: Moreno
authors.forename: Nisha Jain
authors.initials: NJ
authors.lastname: Garg
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D014355:Chagas Disease / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008800:Mexico / Q000453:epidemiology; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D015538:Nitrosation; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000378:metabolism*; D015995:Prevalence; D011506:Proteins / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000276:immunology; D014969:Xanthine Oxidase / Q000097:blood
chemical_list: D000913:Antibodies, Protozoan; D011506:Proteins; D009195:Peroxidase; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D014969:Xanthine Oxidase