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Article: Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

TitleHuman mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo
Authors
KeywordsAcute lung injury
Alveolar fluid clearance
Avian
Influenza
Mesenchymal stromal cells
Issue Date2016
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2016, v. 113 n. 13, p. 3621-3626 How to Cite?
AbstractInfluenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.
Persistent Identifierhttp://hdl.handle.net/10722/224843
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, MCW-
dc.contributor.authorKuok, DIT-
dc.contributor.authorLeung, CYH-
dc.contributor.authorHui, KPY-
dc.contributor.authorDoak, SA-
dc.contributor.authorLau, EHY-
dc.contributor.authorNicholls, JM-
dc.contributor.authorFang, X-
dc.contributor.authorGuan, Y-
dc.contributor.authorLee, JW-
dc.contributor.authorChan, WY-
dc.contributor.authorWebster, RG-
dc.contributor.authorMatthay, MA-
dc.contributor.authorPeiris, JSM-
dc.date.accessioned2016-04-18T03:33:24Z-
dc.date.available2016-04-18T03:33:24Z-
dc.date.issued2016-
dc.identifier.citationProceedings of the National Academy of Sciences, 2016, v. 113 n. 13, p. 3621-3626-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/224843-
dc.description.abstractInfluenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.subjectAcute lung injury-
dc.subjectAlveolar fluid clearance-
dc.subjectAvian-
dc.subjectInfluenza-
dc.subjectMesenchymal stromal cells-
dc.titleHuman mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo-
dc.typeArticle-
dc.identifier.emailChan, MCW: mchan@hku.hk-
dc.identifier.emailLeung, CYH: cyhleung@hku.hk-
dc.identifier.emailHui, KPY: kenrie@hku.hk-
dc.identifier.emailDoak, SA: sophiev@hku.hk-
dc.identifier.emailLau, EHY: ehylau@hku.hk-
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hk-
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hk-
dc.identifier.emailChan, WY: reneewy@hku.hk-
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hk-
dc.identifier.authorityChan, MCW=rp00420-
dc.identifier.authorityLeung, CYH=rp00307-
dc.identifier.authorityDoak, SA=rp02141-
dc.identifier.authorityLau, EHY=rp01349-
dc.identifier.authorityNicholls, JM=rp00364-
dc.identifier.authorityGuan, Y=rp00397-
dc.identifier.authorityChan, WY=rp01596-
dc.identifier.authorityPeiris, JSM=rp00410-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1601911113-
dc.identifier.pmid26976597-
dc.identifier.pmcidPMC4822574-
dc.identifier.scopuseid_2-s2.0-84962128706-
dc.identifier.hkuros257599-
dc.identifier.volume113-
dc.identifier.issue13-
dc.identifier.spage3621-
dc.identifier.epage3626-
dc.identifier.isiWOS:000372876400065-
dc.publisher.placeUnited States-
dc.identifier.issnl0027-8424-

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