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Conference Paper: Angiopoietin-1 and keratinocyte growth factor restore the impaired alveolar fluid clearance induced by influenza H5N1 virus infection

TitleAngiopoietin-1 and keratinocyte growth factor restore the impaired alveolar fluid clearance induced by influenza H5N1 virus infection
Authors
Issue Date2013
PublisherInternational Society for Influenza and other Respiratory Virus Diseases (ISIRV). The Conference Abstracts web site is located at: http://optionsviii.controlinfluenza.com/optionsviii/assets/File/Options_VIII_Abstracts_2013.pdf
Citation
The 2013 International Scientific Conference of Options for the Control of Influenza (Options-8), Cape Town, South Africa, 5-10 September 2013. In Conference Abstracts, 2013, p. 621, abstract no. P2-705 How to Cite?
AbstractBackground: Acute respiratory distress syndrome (ARDS) caused by high pathogenic avian influenza (HPAI) H5N1 virus infection has resulted in severe illness and high mortality rates among patients. Patients with ARDS are often characterized by impaired alveolar fluid clearance and alveolar edema. An understanding of the mechanism responsible for human alveolar edema will lead to the development of novel therapeutic treatments for ARDS patients. We hypothesized that the paracrine soluble factors angiopoietin-1 (Ang-1) and keratinocyte growth factor (KGF) can resolve alveolar fluid clearance by up-regulating the expression of major sodium and chloride transporters impaired by HPAI H5N1 virus infection. Materials and Methods: Human alveolar epithelial cells grown on transwell inserts were infected with HPAI H5N1 (A/HK/483/97) and low pathogenic avian influenza (LPAI) H1N1 (A/HK/54/98) viruses at MOI 0.1 or incubated with conditioned culture medium containing Ang-1 and/or KGF. At 24 and 48 h post-infection, the rate of alveolar fluid transport and protein permeability across the alveolar epithelium was measured. Protein expression of sodium and chloride transporters (Na-K-ATPase, CFTR, and epithelial sodium channel alpha subunit) was measured by qPCR, ELISA, and Western blot. Results: HPAI H5N1 (A/HK/483/97) virus infection significantly reduced net alveolar fluid transport and protein permeability when compared with H1N1 (A/HK/54/98) virus infection at 24 h post-infection and further reduced it at 48 h post-infection. This reduction in alveolar fluid clearance was associated with a substantial reduction in protein expression of Na-K-ATPase, CFTR, and epithelial sodium channel alpha subunit. The influenza virus–infected cells treated with Ang-1 and KGF restored the impaired alveolar edema fluid clearance and protein permeability after HPAI H5N1 virus infection. Furthermore, the paracrine soluble factors Ang-1 and KGF up-regulated the protein expression of the major sodium and chloride transporters resulting from the HPAI influenza virus infection. Conclusions: The paracrine soluble factors Ang-1 and KGF play an important role in maintaining human alveolar fluid clearance by up-regulating the sodium and chloride transporting systems in human alveolar epithelium. This study enriches the understanding of the development of ARDS in human H5N1 disease and may aid in the development of possible therapeutic applications.
DescriptionPoster Session: Novel Therapeutics
Persistent Identifierhttp://hdl.handle.net/10722/188187

 

DC FieldValueLanguage
dc.contributor.authorKuok, ITen_US
dc.contributor.authorChan, WYen_US
dc.contributor.authorLee, JWen_US
dc.contributor.authorFang, Xen_US
dc.contributor.authorMatthay, MAen_US
dc.contributor.authorPeiris, JSMen_US
dc.contributor.authorChan, MCWen_US
dc.date.accessioned2013-08-21T07:43:05Z-
dc.date.available2013-08-21T07:43:05Z-
dc.date.issued2013en_US
dc.identifier.citationThe 2013 International Scientific Conference of Options for the Control of Influenza (Options-8), Cape Town, South Africa, 5-10 September 2013. In Conference Abstracts, 2013, p. 621, abstract no. P2-705en_US
dc.identifier.urihttp://hdl.handle.net/10722/188187-
dc.descriptionPoster Session: Novel Therapeutics-
dc.description.abstractBackground: Acute respiratory distress syndrome (ARDS) caused by high pathogenic avian influenza (HPAI) H5N1 virus infection has resulted in severe illness and high mortality rates among patients. Patients with ARDS are often characterized by impaired alveolar fluid clearance and alveolar edema. An understanding of the mechanism responsible for human alveolar edema will lead to the development of novel therapeutic treatments for ARDS patients. We hypothesized that the paracrine soluble factors angiopoietin-1 (Ang-1) and keratinocyte growth factor (KGF) can resolve alveolar fluid clearance by up-regulating the expression of major sodium and chloride transporters impaired by HPAI H5N1 virus infection. Materials and Methods: Human alveolar epithelial cells grown on transwell inserts were infected with HPAI H5N1 (A/HK/483/97) and low pathogenic avian influenza (LPAI) H1N1 (A/HK/54/98) viruses at MOI 0.1 or incubated with conditioned culture medium containing Ang-1 and/or KGF. At 24 and 48 h post-infection, the rate of alveolar fluid transport and protein permeability across the alveolar epithelium was measured. Protein expression of sodium and chloride transporters (Na-K-ATPase, CFTR, and epithelial sodium channel alpha subunit) was measured by qPCR, ELISA, and Western blot. Results: HPAI H5N1 (A/HK/483/97) virus infection significantly reduced net alveolar fluid transport and protein permeability when compared with H1N1 (A/HK/54/98) virus infection at 24 h post-infection and further reduced it at 48 h post-infection. This reduction in alveolar fluid clearance was associated with a substantial reduction in protein expression of Na-K-ATPase, CFTR, and epithelial sodium channel alpha subunit. The influenza virus–infected cells treated with Ang-1 and KGF restored the impaired alveolar edema fluid clearance and protein permeability after HPAI H5N1 virus infection. Furthermore, the paracrine soluble factors Ang-1 and KGF up-regulated the protein expression of the major sodium and chloride transporters resulting from the HPAI influenza virus infection. Conclusions: The paracrine soluble factors Ang-1 and KGF play an important role in maintaining human alveolar fluid clearance by up-regulating the sodium and chloride transporting systems in human alveolar epithelium. This study enriches the understanding of the development of ARDS in human H5N1 disease and may aid in the development of possible therapeutic applications.-
dc.languageengen_US
dc.publisherInternational Society for Influenza and other Respiratory Virus Diseases (ISIRV). The Conference Abstracts web site is located at: http://optionsviii.controlinfluenza.com/optionsviii/assets/File/Options_VIII_Abstracts_2013.pdf-
dc.relation.ispartofInternational Scientific Conference of Options for the Control of Influenza, Options-8en_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleAngiopoietin-1 and keratinocyte growth factor restore the impaired alveolar fluid clearance induced by influenza H5N1 virus infectionen_US
dc.typeConference_Paperen_US
dc.identifier.emailKuok, IT: dkuok@hku.hken_US
dc.identifier.emailChan, WY: reneewy@hku.hken_US
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_US
dc.identifier.emailChan, MCW: mchan@hku.hken_US
dc.identifier.authorityChan, WY=rp01596en_US
dc.identifier.authorityPeiris, JSM=rp00410en_US
dc.identifier.authorityChan, MCW=rp00420en_US
dc.description.naturepublished_or_final_version-
dc.identifier.hkuros217264en_US
dc.identifier.spage621, abstract no. P2-705-
dc.identifier.epage621, abstract no. P2-705-
dc.publisher.placeUnited Kingdom-

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