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    The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma

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    6
    Author
    Van der Velden, J; Harkness, LM; Barker, DM; Barcham, GJ; Ugalde, CL; Koumoundouros, E; Bao, H; Organ, LA; Tokanovic, A; Burgess, JK; ...
    Date
    2016-05-20
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Organ, Louise; UGALDE, CATHRYN; Snibson, Kenneth; Koumoundouros, Emmanuel; BARKER, DONNA; van der Velden, Joanne; BARCHAM, GARRY
    Affiliation
    Melbourne Veterinary School
    Biomedical Engineering
    Veterinary Biosciences
    Metadata
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    Document Type
    Journal Article
    Citations
    Van der Velden, J., Harkness, L. M., Barker, D. M., Barcham, G. J., Ugalde, C. L., Koumoundouros, E., Bao, H., Organ, L. A., Tokanovic, A., Burgess, J. K. & Snibson, K. J. (2016). The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma. SCIENTIFIC REPORTS, 6 (1), https://doi.org/10.1038/srep26309.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/260468
    DOI
    10.1038/srep26309
    Abstract
    Tumstatin, a protein fragment of the alpha-3 chain of Collagen IV, is known to be significantly reduced in the airways of asthmatics. Further, there is evidence that suggests a link between the relatively low level of tumstatin and the induction of angiogenesis and inflammation in allergic airway disease. Here, we show that the intra-segmental administration of tumstatin can impede the development of vascular remodelling and allergic inflammatory responses that are induced in a segmental challenge model of experimental asthma in sheep. In particular, the administration of tumstatin to lung segments chronically exposed to house dust mite (HDM) resulted in a significant reduction of airway small blood vessels in the diameter range 10(+)-20 μm compared to controls. In tumstatin treated lung segments after HDM challenge, the number of eosinophils was significantly reduced in parenchymal and airway wall tissues, as well as in the bronchoalveolar lavage fluid. The expression of VEGF in airway smooth muscle was also significantly reduced in tumstatin-treated segments compared to control saline-treated segments. Allergic lung function responses were not attenuated by tumstatin administration in this model. The data are consistent with the concept that tumstatin can act to suppress vascular remodelling and inflammation in allergic airway disease.

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