title: The Effects of Tumstatin on Vascularity, Airway Inflammation and Lung Function in an Experimental Sheep Model of Chronic Asthma.
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.
authors.affiliation: Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Van der Velden
authors.affiliation: Woolcock Institute of Medical Research, University of Sydney, NSW, Australia.|Discipline of Pharmacology, The University of Sydney, NSW, Australia.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Harkness
authors.affiliation: Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Australia.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Barker
authors.affiliation: Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Australia.
authors.forename: Garry J
authors.initials: GJ
authors.lastname: Barcham
authors.affiliation: Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Australia.
authors.forename: Cathryn L
authors.initials: CL
authors.lastname: Ugalde
authors.affiliation: Department of Electrical and Electronic Engineering, University of Melbourne, Parkville, Australia.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Koumoundouros
authors.affiliation: Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Australia.
authors.forename: Heidi
authors.initials: H
authors.lastname: Bao
authors.affiliation: Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Australia.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Organ
authors.affiliation: Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Australia.
authors.forename: Ana
authors.initials: A
authors.lastname: Tokanovic
authors.affiliation: Woolcock Institute of Medical Research, University of Sydney, NSW, Australia.|Discipline of Pharmacology, The University of Sydney, NSW, Australia.|University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.affiliation: Faculty of Veterinary and Agricultural Science, University of Melbourne, Parkville, Australia.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Snibson
mesh_terms: D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001324:Autoantigens / Q000008:administration & dosage / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002908:Chronic Disease; D024141:Collagen Type IV / Q000008:administration & dosage / Q000494:pharmacology*; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D009130:Muscle, Smooth / Q000378:metabolism; D034561:Sheep, Domestic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D000485:Allergens; D001324:Autoantigens; D024141:Collagen Type IV; D042461:Vascular Endothelial Growth Factor A; C057112:type IV collagen alpha3 chain