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dc.contributor.authorOshima, Kaori
dc.contributor.authorHan, Xiaorui
dc.contributor.authorOuyang, Yilan
dc.contributor.authorMasri, Rana El
dc.contributor.authorYang, Yimu
dc.contributor.authorHaeger, Sarah M.
dc.contributor.authorMcMurtry, Sarah A.
dc.contributor.authorLane, Trevor C.
dc.contributor.authorDavizon-Castillo, Pavel
dc.contributor.authorZhang, Fuming
dc.contributor.authorYue, Xinping
dc.contributor.authorVivès, Romain R.
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorSchmidt, Eric P.
dc.date2019
dc.date.accessioned2022-06-27T15:46:20Z
dc.date.available2022-06-27T15:46:20Z
dc.date.issued2019-01-01
dc.identifier.citationLoss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses, K. Oshima, X. Han, Y. Ouyang, R. el Masri, Y. Yang, S. Haeger, S. McMurtry, T. Lane, P. Davizon-Castillo, F. Zhang, X. Yue, R. Vivès, R. J. Linhardt, E. Schmidt, American Journal of Physiology-Lung Cellular and Molecular Physiology 317, L667–L677, 2019.
dc.identifier.issn15221504
dc.identifier.issn10400605
dc.identifier.urihttps://doi.org/10.1152/ajplung.00175.2019
dc.identifier.urihttps://hdl.handle.net/20.500.13015/5530
dc.descriptionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology 317, L667–L677
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.abstractSepsis patients are at increased risk for hospital-acquired pulmonary infections, potentially due to postseptic immunosuppression known as the compensatory anti-inflammatory response syndrome (CARS). CARS has been attributed to leukocyte dysfunction, with an unclear role for endothelial cells. The pulmonary circulation is lined by an endothelial glycocalyx, a heparan sulfate-rich layer essential to pulmonary homeostasis. Heparan sulfate degradation occurs early in sepsis, leading to lung injury. Endothelial synthesis of new heparan sulfates subsequently allows for glycocalyx reconstitution and endothelial recovery. We hypothesized that remodeling of the reconstituted endothelial glycocalyx, mediated by alterations in the endothelial machinery responsible for heparan sulfate synthesis, contributes to CARS. Seventy-two hours after experimental sepsis, coincident with glycocalyx reconstitution, mice demonstrated impaired neutrophil and protein influx in response to intratracheal lipopolysaccharide (LPS). The postseptic reconstituted glycocalyx was structurally remodeled, with enrichment of heparan sulfate disaccharides sulfated at the 6-O position of glucosamine. Increased 6-O-sulfation coincided with loss of endothelial sulfatase-1 (Sulf-1), an enzyme that specifically removes 6-O-sulfates from heparan sulfate. Intravenous administration of Sulf-1 to postseptic mice restored the pulmonary response to LPS, suggesting that loss of Sulf-1 was necessary for postseptic suppression of pulmonary inflammation. Endothelial-specific knockout mice demonstrated that loss of Sulf-1 was not sufficient to induce immunosuppression in non-septic mice. Knockdown of Sulf-1 in human pulmonary microvascular endothelial cells resulted in downregulation of the adhesion molecule ICAM-1. Taken together, our study indicates that loss of endothelial Sulf-1 is necessary for postseptic suppression of pulmonary inflammation, representing a novel endothelial contributor to CARS.
dc.description.sponsorshipU.S. Department of Defense
dc.languageen_US
dc.language.isoENG
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
dc.relation.urihttps://harc.rpi.edu/
dc.subjectBiology
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleLoss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses
dc.typeArticle
dcterms.isPartOfJournal
dcterms.isVersionOfhttps://doi.org/10.1152/ajplung.00175.2019
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). https://rightsstatements.org/page/InC/1.0/
dc.creator.identifierhttps://orcid.org/0000-0003-2219-5833
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
rpi.description.pagesL6667-L677
rpi.description.volume317


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