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      Aggravation of ovalbumin-induced murine asthma by co-exposure to desert-dust and organic chemicals: an animal model study

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          Abstract

          Background

          The organic chemicals present in Asian sand dust (ASD) might contribute to the aggravation of lung eosinophila. Therefore, the aggravating effects of the Tar fraction from ASD on ovalbumin (OVA)-induced lung eosinophilia were investigated.

          Methods

          The Tar fraction was extracted from ASD collected from the atmosphere in Fukuoka, Japan. ASD collected from the Gobi desert was heated at 360°C to inactivate toxic organic substances (H-ASD). ICR mice were instilled intratracheally with 12 different test samples prepared with Tar (1 μg and 5 μg), H-ASD, and OVA in a normal saline solution containing 0.02% Tween 80. The lung pathology, cytological profiles in the bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines in BALF and OVA-specific immunoglobulin in serum were investigated.

          Results

          Several kinds of polycyclic aromatic hydrocarbons (PAHs) were detected in the Tar sample. H-ASD + Tar 5 μg induced slight neutrophilic lung inflammation. In the presence of OVA, Tar 5 μg increased the level of eosinophils slightly and induced trace levels of Th2 cytokines IL-5 and IL-13 in BALF. Also mild to moderate goblet cell proliferation and mild infiltration of eosinophils in the submucosa of airway were observed. These pathological changes caused by H-ASD + OVA were relatively small. However, in the presence of OVA and H-ASD, Tar, at as low a level as 1 μg, induced severe eosinophil infiltration and proliferation of goblet cells in the airways and significantly increased Th2 cytokines IL-5 and IL-13 in BALF. The mixture showed an adjuvant effect on OVA-specific IgG1 production.

          Conclusions

          These results indicate that H-ASD with even low levels of Tar exacerbates OVA-induced lung eosinophilia via increases of Th2-mediated cytokines. These results suggest that ASD-bound PAHs might contribute to the aggravation of lung eosinophila.

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          Most cited references43

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          The eosinophil.

          Eosinophils have been considered end-stage cells involved in host protection against parasites. However, numerous lines of evidence have now changed this perspective by showing that eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of diverse inflammatory responses, as well as modulators of innate and adaptive immunity. In this review, we summarize the biology of eosinophils, focusing on the growing properties of eosinophil-derived products, including the constituents of their granules as well as the mechanisms by which they release their pleiotropic mediators. We examine new views on the role of eosinophils in homeostatic function, including developmental biology and innate and adaptive immunity (as well as interaction with mast cells and T cells). The molecular steps involved in eosinophil development and trafficking are described, with special attention to the important role of the transcription factor GATA-1, the eosinophil-selective cytokine IL-5, and the eotaxin subfamily of chemokines. We also review the role of eosinophils in disease processes, including infections, asthma, and gastrointestinal disorders, and new data concerning genetically engineered eosinophil-deficient mice. Finally, strategies for targeted therapeutic intervention in eosinophil-mediated mucosal diseases are conceptualized.
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            Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production.

            Interleukin (IL)-13 is a pleiotropic cytokine produced in large quantities by activated CD4(+) Th2 lymphocytes. To define further its potential in vivo effector functions, the Clara cell 10-kDa protein promoter was used to express IL-13 selectively in the lung, and the phenotype of the resulting transgenic mice was characterized. In contrast to transgene-negative littermates, the lungs of transgene-positive mice contained an inflammatory response around small and large airways and in the surrounding parenchyma. It was mononuclear in nature and contained significant numbers of eosinophils and enlarged and occasionally multinucleated macrophages. Airway epithelial cell hypertrophy, mucus cell metaplasia, the hyperproduction of neutral and acidic mucus, the deposition of Charcot-Leyden-like crystals, and subepithelial airway fibrosis were also prominently noted. Eotaxin protein and mRNA were also present in large quantities in the lungs of the transgene-positive, but not the transgene-negative, mice. IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, and monocyte chemoattractant protein-5 were not similarly detected. Physiological evaluations revealed significant increases in baseline airways resistance and airways hyperresponsiveness (AHR) to methacholine in transgene-positive animals. Thus, the targeted pulmonary expression of IL-13 causes a mononuclear and eosinophilic inflammatory response, mucus cell metaplasia, the deposition of Charcot-Leyden-like crystals, airway fibrosis, eotaxin production, airways obstruction, and nonspecific AHR. IL-13 may play an important role in the pathogenesis of similar responses in asthma or other Th2-polarized tissue responses.
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              Requirement for IL-13 independently of IL-4 in experimental asthma.

              The pathogenesis of asthma reflects, in part, the activity of T cell cytokines. Murine models support participation of interleukin-4 (IL-4) and the IL-4 receptor in asthma. Selective neutralization of IL-13, a cytokine related to IL-4 that also binds to the alpha chain of the IL-4 receptor, ameliorated the asthma phenotype, including airway hyperresponsiveness, eosinophil recruitment, and mucus overproduction. Administration of either IL-13 or IL-4 conferred an asthma-like phenotype to nonimmunized T cell-deficient mice by an IL-4 receptor alpha chain-dependent pathway. This pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL-4 receptor.
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                Author and article information

                Contributors
                455576172@qq.com
                ichinose@oita-nhs.ac.jp
                hemiao@mail.cmu.edu.cn
                arashi@snow.ocn.ne.jp
                freude@med.uoeh-u.ac.jp
                syoshida@oita-nhs.ac.jp
                mnishi@nies.go.jp
                htakano@health.env.kyoto-u.ac.jp
                sungf@mail.cmu.edu.cn
                tshibamoto@ucdavis.edu
                Journal
                Environ Health
                Environ Health
                Environmental Health
                BioMed Central (London )
                1476-069X
                18 October 2014
                18 October 2014
                2014
                : 13
                : 1
                : 83
                Affiliations
                [ ]Department of Nutritional and Food Hygiene, College of Public Health, China Medical University, Shenyang, China
                [ ]Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, Japan
                [ ]Environment and Chronic Non-communicable Disease Research Center, School of Public Health, College of Public Health, China Medical University, 11001 Shenyang, China
                [ ]Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, 807-8555 Fukuoka, Japan
                [ ]Environmental Chemistry Division, National Institute for Environmental Studies, 305-8506 Ibaraki, Japan
                [ ]Environmental Health Division, Department of Environmental Engineering, Graduate School of Engineering, Kyoto University, 615-8530 Kyoto, Japan
                [ ]Department of Environmental Toxicology, University of California, Davis, CA 95616 USA
                Article
                789
                10.1186/1476-069X-13-83
                4216376
                25326908
                c94b6b18-ea11-47d6-87d0-ac7eba6e7eb7
                © Ren et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 3 July 2014
                : 9 October 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Public health
                tar,polycyclic aromatic hydrocarbons,asian sand dust,ovalbumin,lung eosinophilia,cytokine and chemokine

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