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*Chagas Disease

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Clinical and Vaccine Immunology, May 2009, p. 660-666, Vol. 16, No. 5
1071-412X/09/$08.00+0     doi:10.1128/CVI.00019-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease{triangledown}

Monisha Dhiman,1 Jose Guillermo Estrada-Franco,2 Jasmine M. Pando,1 Francisco J. Ramirez-Aguilar,3 Heidi Spratt,4 Sara Vazquez-Corzo,5 Gladys Perez-Molina,5 Rosa Gallegos-Sandoval,6 Roberto Moreno,6 and Nisha Jain Garg1,2,7*

Departments of Microbiology and Immunology,1 Pathology,2 Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555,4 Laboratorio de Enfermedades Emergentes y Zoonóticas, Facultad de Ciencias Químicas—Campus IV, Universidad Autónoma de Chiapas, Tapachula, Chiapas, México,3 Chiapas State Health Services, Chiapas, Mexico,5 Instituto Mexicano del Seguro Social, Chiapas, Mexico,6 The Institute for Human Infections and Immunity, The Center for Biodefense & Emerging Infectious Diseases, and The Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas 775557

Received 14 January 2009/ Returned for modification 11 February 2009/ Accepted 6 March 2009

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 (O2– 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 O2– 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.

* Corresponding author. Mailing address: University of Texas Medical Branch, 3.142C Medical Research Building, 301 University Boulevard, Galveston, TX 77555-1070. Phone: (409) 747-6865. Fax: (409) 747-6869. E-mail: nigarg{at}utmb.edu

{triangledown} Published ahead of print on 18 March 2009.

Clinical and Vaccine Immunology, May 2009, p. 660-666, Vol. 16, No. 5
1071-412X/09/$08.00+0     doi:10.1128/CVI.00019-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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