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dc.contributor.authorHaeger, Sarah M.
dc.contributor.authorLiu, Xinyue
dc.contributor.authorHan, Xiaorui
dc.contributor.authorBrennan McNeil, J.
dc.contributor.authorOshima, Kaori
dc.contributor.authorMcMurtry, Sarah A.
dc.contributor.authorYang, Yimu
dc.contributor.authorOuyang, Yilan
dc.contributor.authorZhang, Fuming
dc.contributor.authorNozik-Grayck, Eva
dc.contributor.authorZemans, Rachel L.
dc.contributor.authorTuder, Rubin M.
dc.contributor.authorBastarache, Julie A.
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorSchmidt, Eric P.
dc.identifier.citationEpithelial Heparan Sulfate Contributes to Alveolar Barrier Function and is Shed during Lung Injury, S. M. Haeger, X. Liu, X. Han, J. B. McNeil, K. Oshima, S. A. McMurtry, Y. Yang, Y. Ouyang, F. Zhang, E. Nozik-Grayck, R. L. Zemans, R. M. Tuder, J. A. Bastarache, R. J. Linhardt, E. P. Schmidt, American Journal of Respiratory Cell and Molecular Biology, 59, 363–374, 2018.
dc.descriptionAmerican Journal of Respiratory Cell and Molecular Biology, 59, 363–374
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractThe lung epithelial glycocalyx is a carbohydrate-enriched layer lining the pulmonary epithelial surface. Although epithelial glycocalyx visualization has been reported, its composition and function remain unknown. Using immunofluorescence and mass spectrometry, we identified heparan sulfate (HS) and chondroitin sulfate within the lung epithelial glycocalyx. In vivo selective enzymatic degradation of epithelial HS, but not chondroitin sulfate, increased lung permeability. Using mass spectrometry and gel electrophoresis approaches to determine the fate of epithelial HS during lung injury, we detected shedding of 20 saccharide-long or greater HS into BAL fluid in intratracheal LPS-treated mice. Furthermore, airspace HS in clinical samples from patients with acute respiratory distress syndrome correlated with indices of alveolar permeability, reflecting the clinical relevance of these findings. The length of HS shed during intratracheal LPS-induced injury (≥20 saccharides) suggests cleavage of the proteoglycan anchoring HS to the epithelial surface, rather than cleavage of HS itself. We used pharmacologic and transgenic animal approaches to determine that matrix metalloproteinases partially mediate HS shedding during intratracheal LPS-induced lung injury. Although there was a trend toward decreased alveolar permeability after treatment with the matrix metalloproteinase inhibitor, doxycycline, this did not reach statistical significance. These studies suggest that epithelial HS contributes to the lung epithelial barrier and its degradation is sufficient to increase lung permeability. The partial reduction of HS shedding achieved with doxycycline is not sufficient to rescue epithelial barrier function during intratracheal LPS-induced lung injury; however, whether complete attenuation of HS shedding is sufficient to rescue epithelial barrier function remains unknown.
dc.description.sponsorshipNational Institutes of Health
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofAmerican Journal of Respiratory Cell and Molecular Biology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleEpithelial Heparan Sulfate Contributes to Alveolar Barrier Function and is Shed during Lung Injury
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)

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