期刊论文详细信息
Respiratory Research
Increase of nitrosative stress in patients with eosinophilic pneumonia
Masakazu Ichinose1  Manabu Nishigai2  Masae Kanda1  Keiichiro Akamatsu1  Yoshiaki Minakata1  Satoru Yanagisawa1  Tsunahiko Hirano1  Akira Koarai1  Tomohiro Ichikawa1  Kazuto Matsunaga1  Hisatoshi Sugiura1  Kanako Furukawa1 
[1] Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan;Chest M.I., Inc., 3-6-10 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
关键词: 3-nitrotyrosine;    inducible type of nitric oxide synthase;    fractional exhaled nitric oxide;    corticosteroid;    Alveolar nitric oxide;   
Others  :  796841
DOI  :  10.1186/1465-9921-12-81
 received in 2011-02-28, accepted in 2011-06-17,  发布年份 2011
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【 摘 要 】

Background

Exhaled nitric oxide (NO) production is increased in asthma and reflects the degree of airway inflammation. The alveolar NO concentration (Calv) in interstitial pneumonia is reported to be increased. However, it remains unknown whether NO production is increased and nitrosative stress occurs in eosinophilic pneumonia (EP). We hypothesized that nitrosative stress markers including Calv, inducible type of NO synthase (iNOS), and 3-nitrotyrosine (3-NT), are upregulated in EP.

Methods

Exhaled NO including fractional exhaled NO (FENO) and Calv was measured in ten healthy subjects, 13 patients with idiopathic pulmonary fibrosis (IPF), and 13 patients with EP. iNOS expression and 3-NT formation were assessed by immunocytochemistory in BALf cells. The exhaled NO, lung function, and systemic inflammatory markers of the EP patients were investigated after corticosteroid treatment for 4 weeks.

Results

The Calv levels in the EP group (14.4 ± 2.0 ppb) were significantly higher than those in the healthy subjects (5.1 ± 0.6 ppb, p < 0.01) and the IPF groups (6.3 ± 0.6 ppb, p < 0.01) as well as the FENO and the corrected Calv levels (all p < 0.01). More iNOS and 3-NT positive cells were observed in the EP group compared to the healthy subject and IPF patient. The Calv levels had significant positive correlations with both iNOS (r = 0.858, p < 0.05) and 3-NT positive cells (r = 0.924, p < 0.01). Corticosteroid treatment significantly reduced both the FENO (p < 0.05) and the Calv levels (p < 0.01). The magnitude of reduction in the Calv levels had a significant positive correlation with the peripheral blood eosinophil counts (r = 0.802, p < 0.05).

Conclusions

These results suggested that excessive nitrosative stress occurred in EP and that Calv could be a marker of the disease activity.

【 授权许可】

   
2011 Furukawa et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Jeong YJ, Kim KI, Seo IJ, Lee CH, Lee KN, Kim KN, Kim JS, Kwon WJ: Eosinophilic lung diseases: a clinical, radiologic, and pathologic overview. Radiographics 2007, 27:617-637.
  • [2]Allen JN, Davis WB: Eosinophilic lung diseases. Am J Respir Crit Care Med 1994, 150:1423-1438.
  • [3]Nakahara Y, Hayashi S, Fukuno Y, Kawashima M, Yatsunami J: Increased interleukin-5 levels in bronchoalveolar lavage fluid is a major factor for eosinophil accumulation in acute eosinophilic pneumonia. Respiration 2001, 68:389-395.
  • [4]Taniguchi H, Katoh S, Kadota J, Matsubara Y, Fukushima K, Mukae H, Matsukura S, Kohno S: Interleukin 5 and granulocyte-macrophage colony-stimulating factor levels in bronchoalveolar lavage fluid in interstitial lung disease. Eur Respir J 2000, 16:959-964.
  • [5]Katoh S, Matsumoto N, Matsumoto K, Fukushima K, Matsukura S: Elevated interleukin-18 levels in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia. Allergy 2004, 59:850-856.
  • [6]Gleich GJ, Adolphson CR, Leiferman KM: The biology of the eosinophilic leukocyte. Annu Rev Med 1993, 44:85-101.
  • [7]Hamid Q, Springall DR, Riveros-Moreno V, Chanez P, Howarth P, Redington A, Bousquet J, Godard P, Holgate S, Polak JM: Induction of nitric oxide synthase in asthma. Lancet 1993, 342:1510-1513.
  • [8]Sugiura H, Ichinose M: Oxidative and nitrative stress in bronchial asthma. Antioxid Redox Signal 2008, 10:785-797.
  • [9]Moncada S, Higgs A: The L-arginine-nitric oxide pathway. N Engl J Med 1993, 329:2002-2012.
  • [10]Shult PA, Graziano FM, Busse WW: Enhanced eosinophil luminol-dependent chemiluminescence in allergic rhinitis. J Allergy Clin Immunol 1986, 77:702-708.
  • [11]Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA: Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 1990, 87:1620-1624.
  • [12]Marshall HE, Merchant K, Stamler JS: Nitrosation and oxidation in the regulation of gene expression. FASEB J 2000, 14:1889-1900.
  • [13]Sugiura H, Ichinose M, Oyake T, Mashito Y, Ohuchi Y, Endoh N, Miura M, Yamagata S, Koarai A, Akaike T, Maeda H, Shirato K: Role of peroxynitrite in airway microvascular hyperpermeability during late allergic phase in guinea pigs. Am J Respir Crit Care Med 1999, 160:663-671.
  • [14]Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne EA, Barnes PJ: Increased nitric oxide in exhaled air of asthmatic patients. Lancet 1994, 343:133-135.
  • [15]Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ: Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax 1998, 53:91-95.
  • [16]Ichinose M, Takahashi T, Sugiura H, Endoh N, Miura M, Mashito Y, Shirato K: Baseline airway hyperresponsiveness and its reversible component: role of airway inflammation and airway calibre. Eur Respir J 2000, 15:248-253.
  • [17]Tsoukias NM, George SC: A two-compartment model of pulmonary nitric oxide exchange dynamics. J Appl Physiol 1998, 85:653-666.
  • [18]Lehtimaki L, Kankaanranta H, Saarelainen S, Hahtola P, Jarvenpaa R, Koivula T, Turjanmaa V, Moilanen E: Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation. Am J Respir Crit Care Med 2001, 163:1557-1561.
  • [19]American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) was adopted by the ATS board of directors June 2001 and by the ERS Executive Committee June 2001 Am J Respir Crit Care Med 2002, 165:277-304.
  • [20]ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide 2005 Am J Respir Crit Care Med 2005, 171:912-930.
  • [21]Condorelli P, Shin HW, Aledia AS, Silkoff PE, George SC: A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model. J Appl Physiol 2007, 102:417-425.
  • [22]Piotrowski WJ, Antczak A, Marczak J, Nawrocka A, Kurmanowska Z, Gorski P: Eicosanoids in exhaled breath condensate and BAL fluid of patients with sarcoidosis. Chest 2007, 132:589-596.
  • [23]Ichinose M, Sugiura H, Yamagata S, Koarai A, Shirato K: Increase in reactive nitrogen species production in chronic obstructive pulmonary disease airways. Am J Respir Crit Care Med 2000, 162:701-706.
  • [24]Horvath I, Hunt J, Barnes PJ, Alving K, Antczak A, Baraldi E, Becher G, van Beurden WJ, Corradi M, Dekhuijzen R, Dweik RA, Dwyer T, Effros R, Erzurum S, Gaston B, Gessner C, Greening A, Ho LP, Hohlfeld J, Jöbsis Q, Laskowski D, Loukides S, Marlin D, Montuschi P, Olin AC, Redington AE, Reinhold P, van Rensen EL, Rubinstein I, Silkoff P, et al.: Exhaled breath condensate: methodological recommendations and unresolved questions. Eur Respir J 2005, 26:523-548.
  • [25]Eiserich JP, Hristova M, Cross CE, Jones AD, Freeman BA, Halliwell B, van der Vliet A: Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 1998, 391:393-397.
  • [26]Pryor WA, Squadrito GL: The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 1995, 268:L699-722.
  • [27]Sugiura H, Liu X, Kobayashi T, Togo S, Ertl RF, Kawasaki S, Kamio K, Wang XQ, Mao L, Shen L, Hogaboam CM, Rennard SI: Reactive nitrogen species augment fibroblast-mediated collagen gel contraction, mediator production, and chemotaxis. Am J Respir Cell Mol Biol 2006, 34:592-599.
  • [28]Ichikawa T, Sugiura H, Koarai A, Yanagisawa S, Kanda M, Hayata A, Furukawa K, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M: Peroxynitrite augments fibroblast-mediated tissue remodeling via myofibroblast differentiation. Am J Physiol Lung Cell Mol Physiol 2008, 295:L800-808.
  • [29]Hobbs AJ, Higgs A, Moncada S: Inhibition of nitric oxide synthase as a potential therapeutic target. Annu Rev Pharmacol Toxicol 1999, 39:191-220.
  • [30]Zanardo RC, Costa E, Ferreira HH, Antunes E, Martins AR, Murad F, De Nucci G: Pharmacological and immunohistochemical evidence for a functional nitric oxide synthase system in rat peritoneal eosinophils. Proc Natl Acad Sci USA 1997, 94:14111-14114.
  • [31]Hebestreit H, Dibbert B, Balatti I, Braun D, Schapowal A, Blaser K, Simon HU: Disruption of fas receptor signaling by nitric oxide in eosinophils. J Exp Med 1998, 187:415-425.
  • [32]Okamoto T, Akuta T, Tamura F, van Der Vliet A, Akaike T: Molecular mechanism for activation and regulation of matrix metalloproteinases during bacterial infections and respiratory inflammation. Biol Chem 2004, 385:997-1006.
  • [33]Brindicci C, Kharitonov SA, Ito M, Elliott MW, Hogg JC, Barnes PJ, Ito K: Nitric oxide synthase isoenzyme expression and activity in peripheral lung tissue of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010, 181:21-30.
  • [34]Radomski MW, Palmer RM, Moncada S: Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells. Proc Natl Acad Sci USA 1990, 87:10043-10047.
  • [35]Matsunaga K, Yanagisawa S, Ichikawa T, Ueshima K, Akamatsu K, Hirano T, Nakanishi M, Yamagata T, Minakata Y, Ichinose M: Airway cytokine expression measured by means of protein array in exhaled breath condensate: correlation with physiologic properties in asthmatic patients. J Allergy Clin Immunol 2006, 118:84-90.
  • [36]Montuschi P, Macagno F, Parente P, Valente S, Lauriola L, Ciappi G, Kharitonov SA, Barnes PJ, Ciabattoni G: Effects of cyclo-oxygenase inhibition on exhaled eicosanoids in patients with COPD. Thorax 2005, 60:827-833.
  • [37]Choi J, Hoffman LA, Sethi JM, Zullo TG, Gibson KF: Multiple flow rates measurement of exhaled nitric oxide in patients with sarcoidosis: a pilot feasibility study. Sarcoidosis Vasc Diffuse Lung Dis 2009, 26:98-109.
  • [38]Sepponen A, Lehtimaki L, Huhtala H, Kaila M, Kankaanranta H, Moilanen E: Alveolar and bronchial nitric oxide output in healthy children. Pediatr Pulmonol 2008, 43:1242-1248.
  • [39]Saleh D, Barnes PJ, Giaid A: Increased production of the potent oxidant peroxynitrite in the lungs of patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1997, 155:1763-1769.
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