| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,*,*
Departments of
*
Cell Biology,
Cardiology,
Cancer Biology,
Pulmonary and Critical Care Medicine, and
¶
Center for Cardiovascular Diagnostics, Cleveland Clinic Foundation, Cleveland, OH 44195;
||
Cleveland State University, Department of Chemistry, Cleveland, OH 44115;
#
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131; and
**
Quest Diagnostics, San Juan Capistrano, CA 92690
Department of Cell Biology,
*
Department of Cardiology,
*
Department of Cancer Biology,
*
Department of Pulmonary and Critical Care Medicine, and
*
Center for Cardiovascular Diagnostics, Cleveland Clinic Foundation, Cleveland, OH 44195;
*
Cleveland State University, Department of Chemistry, Cleveland, OH 44115;
*
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131; and
*
Quest Diagnostics, San Juan Capistrano, CA 92690
Eosinophil recruitment and enhanced production of NO are characteristic features of asthma. However, neither the ability of eosinophils to generate NO-derived oxidants nor their role in nitration of targets during asthma is established. Using gas chromatography-mass spectrometry we demonstrate a 10-fold increase in 3-nitrotyrosine (NO2Y) content, a global marker of protein modification by reactive nitrogen species, in proteins recovered from bronchoalveolar lavage of severe asthmatic patients (480 ± 198 µmol/mol tyrosine; n = 11) compared with nonasthmatic subjects (52.5 ± 40.7 µmol/mol tyrosine; n = 12). Parallel gas chromatography-mass spectrometry analyses of bronchoalveolar lavage proteins for 3-bromotyrosine (BrY) and 3-chlorotyrosine (ClY), selective markers of eosinophil peroxidase (EPO)- and myeloperoxidase-catalyzed oxidation, respectively, demonstrated a dramatic preferential formation of BrY in asthmatic (1093 ± 457 µmol BrY/mol tyrosine; 161 ± 88 µmol ClY/mol tyrosine; n = 11 each) compared with nonasthmatic subjects (13 ± 14.5 µmol BrY/mol tyrosine; 65 ± 69 µmol ClY/mol tyrosine; n = 12 each). Bronchial tissue from individuals who died of asthma demonstrated the most intense anti-NO2Y immunostaining in epitopes that colocalized with eosinophils. Although eosinophils from normal subjects failed to generate detectable levels of NO, NO2-, NO3-, or NO2Y, tyrosine nitration was promoted by eosinophils activated either in the presence of physiological levels of NO2- or an exogenous NO source. At low, but not high (e.g., >2 µM/min), rates of NO flux, EPO inhibitors and catalase markedly attenuated aromatic nitration. These results identify eosinophils as a major source of oxidants during asthma. They also demonstrate that eosinophils use distinct mechanisms for generating NO-derived oxidants and identify EPO as an enzymatic source of nitrating intermediates in eosinophils.
This article has been cited by other articles:
|
|
 |
|
  A. Nadeem, A. Masood, and N. Siddiqui Review: Oxidant--antioxidant imbalance in asthma: scientific evidence, epidemiological data and possible therapeutic options Therapeutic Advances in Respiratory Disease, August 1, 2008; 2(4): 215 - 235. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Wehling-Henricks, S. Sokolow, J. J. Lee, K. H. Myung, S. A. Villalta, and J. G. Tidball Major basic protein-1 promotes fibrosis of dystrophic muscle and attenuates the cellular immune response in muscular dystrophy Hum. Mol. Genet., August 1, 2008; 17(15): 2280 - 2292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ghosh, A. J. Janocha, M. A. Aronica, S. Swaidani, S. A. A. Comhair, W. Xu, L. Zheng, S. Kaveti, M. Kinter, S. L. Hazen, et al. Nitrotyrosine Proteome Survey in Asthma Identifies Oxidative Mechanism of Catalase Inactivation J. Immunol., May 1, 2006; 176(9): 5587 - 5597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Dalle-Donne, R. Rossi, R. Colombo, D. Giustarini, and A. Milzani Biomarkers of Oxidative Damage in Human Disease Clin. Chem., April 1, 2006; 52(4): 601 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang, Y. Xu, J. Joseph, and B. Kalyanaraman Intramolecular Electron Transfer between Tyrosyl Radical and Cysteine Residue Inhibits Tyrosine Nitration and Induces Thiyl Radical Formation in Model Peptides Treated with Myeloperoxidase, H2O2, and NO2-: EPR SPIN TRAPPING STUDIES J. Biol. Chem., December 9, 2005; 280(49): 40684 - 40698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. A. Comhair, K. S. Ricci, M. Arroliga, A. R. Lara, R. A. Dweik, W. Song, S. L. Hazen, E. R. Bleecker, W. W. Busse, K. F. Chung, et al. Correlation of Systemic Superoxide Dismutase Deficiency to Airflow Obstruction in Asthma Am. J. Respir. Crit. Care Med., August 1, 2005; 172(3): 306 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. P. Kurup, R. Raju, and P. Manickam Profile of Gene Expression in a Murine Model of Allergic Bronchopulmonary Aspergillosis Infect. Immun., July 1, 2005; 73(7): 4381 - 4384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A.A. Comhair, W. Xu, S. Ghosh, F. B.J.M. Thunnissen, A. Almasan, W. J. Calhoun, A. J. Janocha, L. Zheng, S. L. Hazen, and S. C. Erzurum Superoxide Dismutase Inactivation in Pathophysiology of Asthmatic Airway Remodeling and Reactivity Am. J. Pathol., March 1, 2005; 166(3): 663 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Davis, B. F. Flanagan, A. M. Gilfillan, D. D. Metcalfe, and J. W. Coleman Nitric Oxide Inhibits IgE-Dependent Cytokine Production and Fos and Jun Activation in Mast Cells J. Immunol., December 1, 2004; 173(11): 6914 - 6920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Koeck, X. Fu, S. L. Hazen, J. W. Crabb, D. J. Stuehr, and K. S. Aulak Rapid and Selective Oxygen-regulated Protein Tyrosine Denitration and Nitration in Mitochondria J. Biol. Chem., June 25, 2004; 279(26): 27257 - 27262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Koeck, B. Levison, S. L. Hazen, J. W. Crabb, D. J. Stuehr, and K. S. Aulak Tyrosine Nitration Impairs Mammalian Aldolase A Activity Mol. Cell. Proteomics, June 1, 2004; 3(6): 548 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Forbes, T. Murase, M. Yang, K. I. Matthaei, J. J. Lee, N. A. Lee, P. S. Foster, and S. P. Hogan Immunopathogenesis of Experimental Ulcerative Colitis Is Mediated by Eosinophil Peroxidase J. Immunol., May 1, 2004; 172(9): 5664 - 5675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Mahut, C. Delacourt, F. Zerah-Lancner, J. De Blic, A. Harf, and C. Delclaux Increase in Alveolar Nitric Oxide in the Presence of Symptoms in Childhood Asthma Chest, March 1, 2004; 125(3): 1012 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Caramori and A Papi Oxidants and asthma Thorax, February 1, 2004; 59(2): 170 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. McElhinney, M. E. Poynter, P. Shrivastava, S. L. Hazen, and Y. M. W. Janssen-Heininger Eosinophil peroxidase catalyzes JNK-mediated membrane blebbing in a Rho kinase-dependent manner J. Leukoc. Biol., November 1, 2003; 74(5): 897 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Fries, E. Paxinou, M. Themistocleous, E. Swanberg, K. K. Griendling, D. Salvemini, J. W. Slot, H. F. G. Heijnen, S. L. Hazen, and H. Ischiropoulos Expression of Inducible Nitric-oxide Synthase and Intracellular Protein Tyrosine Nitration in Vascular Smooth Muscle Cells: ROLE OF REACTIVE OXYGEN SPECIES J. Biol. Chem., June 13, 2003; 278(25): 22901 - 22907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. C. Koo, K. Shah, G. J. F. Ding, J. Xiao, R. Wnek, G. Doherty, X. C. Tong, R. B. Pepinsky, K.-C. Lin, W. K. Hagmann, et al. A Small Molecule Very Late Antigen-4 Antagonist Can Inhibit Ovalbumin-induced Lung Inflammation Am. J. Respir. Crit. Care Med., May 15, 2003; 167(10): 1400 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Albert, A. K. Thukkani, R. M. Heuertz, A. Slungaard, S. L. Hazen, and D. A. Ford Eosinophil Peroxidase-derived Reactive Brominating Species Target the Vinyl Ether Bond of Plasmalogens Generating a Novel Chemoattractant, alpha -Bromo Fatty Aldehyde J. Biol. Chem., March 7, 2003; 278(11): 8942 - 8950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P A Steerenberg, N A H Janssen, G de Meer, P H Fischer, S Nierkens, H van Loveren, A Opperhuizen, B Brunekreef, and J G C van Amsterdam Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children Thorax, March 1, 2003; 58(3): 242 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Nguyen, J.-L. Teo, A. Matsuda, M. Eguchi, E. Y. Chi, W. R. Henderson Jr., and M. Kahn Chemogenomic identification of Ref-1/AP-1 as a therapeutic target for asthma PNAS, February 4, 2003; 100(3): 1169 - 1173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Bowler and J. D. Crapo Oxidative Stress in Airways: Is There a Role for Extracellular Superoxide Dismutase? Am. J. Respir. Crit. Care Med., December 15, 2002; 166(12): S38 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Koarai, M. Ichinose, H. Sugiura, M. Tomaki, M. Watanabe, S. Yamagata, Y. Komaki, K. Shirato, and T. Hattori iNOS depletion completely diminishes reactive nitrogen-species formation after an allergic response Eur. Respir. J., September 1, 2002; 20(3): 609 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zhang, Z. Shen, W. M. Nauseef, and S. L. Hazen Defects in leukocyte-mediated initiation of lipid peroxidation in plasma as studied in myeloperoxidase-deficient subjects: systematic identification of multiple endogenous diffusible substrates for myeloperoxidase in plasma Blood, March 1, 2002; 99(5): 1802 - 1810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. TERADA, T. FUJISAWA, K. TOGASHI, T. MIYAZAKI, H. KATSUMATA, J. ATSUTA, K. IGUCHI, H. KAMIYA, and H. TOGARI Exhaled Nitric Oxide Decreases during Exercise-induced Bronchoconstriction in Children with Asthma Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1879 - 1884. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Cross, A. van der Vliet, and J. P. Eiserich Peroxidases Wheezing Their Way into Asthma Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1102 - 1103. [Full Text] [PDF]
|
|
|
|
|
|
K. L. Denzler, M. T. Borchers, J. R. Crosby, G. Cieslewicz, E. M. Hines, J. P. Justice, S. A. Cormier, K. A. Lindenberger, W. Song, W. Wu, et al. Extensive Eosinophil Degranulation and Peroxidase-Mediated Oxidation of Airway Proteins Do Not Occur in a Mouse Ovalbumin-Challenge Model of Pulmonary Inflammation J. Immunol., August 1, 2001; 167(3): 1672 - 1682. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
