B7H3 ameliorates LPS-induced acute lung injury via attenuation of neutrophil migration and infiltration

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dc.contributor.authorLi, Yan
dc.contributor.authorHuang, Jie
dc.contributor.authorFoley, Niamh M.
dc.contributor.authorXu, Yunyun
dc.contributor.authorLi, Yi Ping
dc.contributor.authorPan, Jian
dc.contributor.authorRedmond, H. Paul
dc.contributor.authorWang, Jiang Huai
dc.contributor.authorWang, Jian
dc.contributor.funderNational Natural Science Foundation of Chinaen
dc.contributor.funderNatural Science Foundation of Jiangsu Provinceen
dc.contributor.funderJiangsu Innovation Team. Chinaen
dc.contributor.funderJiangsu Province Program of Innovative and Entrepreneurial Talents, Chinaen
dc.date.accessioned2017-04-03T14:10:29Z
dc.date.available2017-04-03T14:10:29Z
dc.date.issued2016-08
dc.date.updated2017-04-03T14:04:47Z
dc.description.abstractAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by an excessive inflammatory response within the lungs and severely impaired gas exchange resulting from alveolar-capillary barrier disruption and pulmonary edema. The costimulatory protein B7H3 functions as both a costimulator and coinhibitor to regulate the adaptive and innate immune response, thus participating in the development of microbial sepsis and pneumococcal meningitis. However, it is unclear whether B7H3 exerts a beneficial or detrimental role during ALI. In the present study we examined the impact of B7H3 on pulmonary inflammatory response, polymorphonuclear neutrophil (PMN) influx, and lung tissue damage in a murine model of lipopolysaccharide (LPS)-induced direct ALI. Treatment with B7H3 protected mice against LPS-induced ALI, with significantly attenuated pulmonary PMN infiltration, decreased lung myeloperoxidase (MPO) activity, reduced bronchoalveolar lavage fluid (BALF) protein content, and ameliorated lung pathological changes. In addition, B7H3 significantly diminished LPS-stimulated PMN chemoattractant CXCL2 production by inhibiting NF-kappa B p65 phosphorylation, and substantially attenuated LPS-induced PMN chemotaxis and transendothelial migration by down-regulating CXCR2 and Mac-1 expression. These results demonstrate that B7H3 substantially ameliorates LPS-induced ALI and this protection afforded by B7H3 is predominantly associated with its inhibitory effect on pulmonary PMN migration and infiltration.en
dc.description.sponsorshipNational Natural Science Foundation of China (Grants 81272143 and 81420108022); Natural Science Foundation of Jiangsu Province (Grant BK2011310); Jiangsu Innovation Team (Grant LJ201141); Jiangsu Province Program of Innovative and Entrepreneurial Talents (2011–2014)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLi, Y., Huang, J., Foley, N. M., Xu, Y., Li, Y. P., Pan, J., Redmond, H. P., Wang, J. H. and Wang, J. (2016) 'B7H3 ameliorates LPS-induced acute lung injury via attenuation of neutrophil migration and infiltration', Scientific Reports, 6, 31284. DOI: 10.1038/srep31284en
dc.identifier.doi10.1038/srep31284
dc.identifier.issn2045-2322
dc.identifier.journaltitleScientific Reportsen
dc.identifier.urihttps://hdl.handle.net/10468/3853
dc.identifier.volume6en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urihttp://www.nature.com/articles/srep31284
dc.rights© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectRespiratory-distress-syndromeen
dc.subjectInucible Nitric-Oxideen
dc.subjectT-cellsen
dc.subjectInflammatory responseen
dc.subjectDendritic cellsen
dc.subjectB7-H3en
dc.subjectFamilyen
dc.subjectSepsisen
dc.subjectMiceen
dc.subjectLipopolysaccharideen
dc.titleB7H3 ameliorates LPS-induced acute lung injury via attenuation of neutrophil migration and infiltrationen
dc.typeArticle (peer-reviewed)en
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