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Identification of Annexin II as a carbohydrate associated novel mediator of airway epithelial would repair

University of British Columbia

Epithelial cells line the conducting airways of the lung and act as a protective barrier to the daily challenges such as viral particles, pollutants and allergens. As a result, the epithelium is routinely damaged which is followed by rapid and effective repair. This highlights the importance of understanding the mechanisms involved in normal airway epithelial repair such that diseases like asthma can be better understood. Our laboratory has highlighted the role of carbohydrates structural modification as essential in mediating epithelial repair. The identity of the functional carbohydrate structures and their associated protein(s) remain unknown. The principal goals of my research were to take a glycomics based approach to identify mediators of airway epithelial repair. This work is broken down into three sections where we (1) investigated the identity of the Cicer arietinum agglutinin (CPA) associated protein ligand, (2) investigated the identity of the Allomyrina dichotoma agglutinin (AlloA) associated protein ligand on the surface of airway epithelial cells, and (3) began to characterize their potential role in airway epithelial wound repair. We have identified two novel carbohydrate epitopes using the lectins CPA and AlloA and their associated proteins as candidates that participate in airway epithelial wound repair. Using CPA to precipitate lectin associated protein(s), Annexin II (AII) was isolated and enriched when precipitated from wounded monolayers of airway epithelial cells. The expression of AII and its presentation on the surface of epithelial cells closely resembled our initial cell surface CPA staining. Simultaneous work identified fetuin as an AlloA associated protein. Fetuin is a serum glycoprotein previously shown to bind AII on the surface of epithelial cells. Our subsequent work focused on the role of AII, specifically cell surface AII, in this process. As a receptor for tenascin-C, we followed wound repair activation following AII/tenascin-C binding in our model of repair. We found that AII facilitated tenascin-C binding which stimulated epithelial cell wound closure rates. This study is the first to identify AII as a mediator of epithelial wound repair and identify the potential role of cell surface AII as a receptor for tenascin-C binding.

Thesis/Dissertation

application/pdf

2009-06-03

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/8659

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/