Mononuclear Phagocyte Xanthine Oxidoreductase Contributes to Cytokine-Induced Acute Lung Injury
| Autor: | Noi Kosila, Richard M. Wright, Brendan Essary, James L. McManaman, Lisa A. Ginger, John E. Repine, Nancy D. Elkins |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Xanthine Oxidase Allopurinol medicine.medical_treatment Clinical Biochemistry Apoptosis Inflammation Biology Lung injury Tungsten Rats Sprague-Dawley Alveolar cells Interferon-gamma chemistry.chemical_compound medicine Animals Macrophage Enzyme Inhibitors Lung Molecular Biology Phagocytes Respiratory Distress Syndrome medicine.diagnostic_test Nitrotyrosine Cell Differentiation Pneumonia Cell Biology respiratory system Rats respiratory tract diseases Pulmonary Alveoli Cytokine Bronchoalveolar lavage medicine.anatomical_structure chemistry Enzyme Induction Immunology Cytokines Tyrosine Tumor necrosis factor alpha medicine.symptom Interleukin-1 |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 30:479-490 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | Acute lung injury (ALI) is characterized by increased alveolar cytokines, inflammatory cell infiltration, oxidative stress, and alveolar cell apoptosis. Previous work suggested that xanthine oxidoreductase (XOR) may contribute to oxidative stress in ALI as a product of the vascular endothelial cell. We present evidence that cytokine induced lung inflammation and injury involves activation of XOR in the newly recruited mononuclear phagocytes (MNP). We found that XOR was increased predominantly in the MNP that increase rapidly in the lungs of rats that develop ALI following intratracheal cytokine insufflation. XOR was recovered from the MNP largely converted to its oxygen radical generating, reversible O-form, and alveolar MNP exhibited increased oxidative stress as evidenced by increased nitrotyrosine staining. Cytokine insufflation also increased alveolar cell apoptosis. A functional role for XOR in cytokine-induced inflammation was demonstrated when feeding rats two different XOR inhibitors, tungsten and allopurinol, decreased MNP XOR induction, nitrotyrosine staining, inflammatory cell infiltration, and alveolar cell apoptosis. Transfer of control or allopurinol treated MNP into rat lungs confirmed a specific role for MNP XOR in promoting lung inflammation. These data indicate that XOR can contribute to lung inflammation by its expression and conversion in a highly mobile inflammatory cell population. Acute lung injury (ALI) is a highly fatal inflammatory disorder characterized by increased alveolar cytokine expression, neutrophil and monocyte recruitment into the lung, macrophage activation, oxidative stress, alveolar cell apoptosis, and lung edema (1, 2). Bronchoalveolar lavage fluid (BALF) from patients with ALI contains increased concentrations of numerous cytokines and chemokines including interleukin (IL)-1, interferon (IFN)-, IL-6, IL-8, tumor necrosis factor-, IL-10, transforming growth factor-, and monocyte chemotactic protein (MCP)-1 (3‐5). Although the contribution of individual cytokines to the pathophysiology of ALI is not understood, intratracheal insufflation of IL-1 in rats produces lung inflammation with many characteris |
| Databáze: | OpenAIRE |
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