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dc.contributor.authorBozinovski, S
dc.contributor.authorCross, M
dc.contributor.authorVlahos, R
dc.contributor.authorJones, JE
dc.contributor.authorHsuu, K
dc.contributor.authorTessier, PA
dc.contributor.authorReynolds, EC
dc.contributor.authorHume, DA
dc.contributor.authorHamilton, JA
dc.contributor.authorGeczy, CL
dc.contributor.authorAnderson, GP
dc.date.available2014-05-21T19:20:07Z
dc.date.issued2005-01-01
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000227287000016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=d4d813f4571fa7d6246bdc0dfeca3a1c
dc.identifier.citationBozinovski, S., Cross, M., Vlahos, R., Jones, J. E., Hsuu, K., Tessier, P. A., Reynolds, E. C., Hume, D. A., Hamilton, J. A., Geczy, C. L. & Anderson, G. P. (2005). S100A8 chemotactic protein is abundantly increased, but only a minor contributor to LPS-induced, steroid resistant neutrophilic lung inflammation in vivo. JOURNAL OF PROTEOME RESEARCH, 4 (1), pp.136-145. https://doi.org/10.1021/pr049829t.
dc.identifier.issn1535-3893
dc.identifier.urihttp://hdl.handle.net/11343/26124
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractNeutrophilic lung inflammation is an essential component of host defense against diverse eukaryotic and prokaryotic pathogens, but in chronic inflammatory lung diseases, such as chronic obstructive lung disease (COPD), severe asthma, cystic fibrosis, and bronchiolitis, it may damage the host. Glucocorticosteroids are widely used in these conditions and in their infectious exacerbations; however, the clinical efficacy of steroids is disputed. In this study, we used a proteomic approach to identify molecules contributing to neutrophilic inflammation induced by transnasal administration of lipopolysaccharide (LPS) that were also resistant to the potent glucocorticosteroid dexamethasone (Dex). We confirmed that Dex was biologically active at both the transcript (suppression of GM-CSF and TNFalphatranscripts) and protein levels (induction of lipocortin) and used 2D-PAGE/MALDI-TOF to generate global expression profiles, identifying six LPS-induced proteins that were Dex resistant. Of these, S100A8, a candidate neutrophil chemotactic factor, was profiled in detail. Steroid refractory S100A8 expression was highly abundant, transcriptionally regulated, secreted into lung lavage fluid and immunohistochemically localized to tissue infiltrating neutrophils. However, in marked contrast to other vascular beds, neutralizing antibodies to S100A8 had only a weak anti-neutrophil recruitment effect and antibodies against the related S100A9 were ineffective. These data highlight the need for extensive in vivo profiling of proteomically identified candidate molecules and demonstrates that S100A8, despite its abundance, resistance to steroids and known chemotactic activity, is unlikely to be an important determinant of LPS-induced neutrophilic lung inflammation in vivo.
dc.languageEnglish
dc.publisherAMER CHEMICAL SOC
dc.subjectMedical Biochemistry: Proteins and Peptides; Endocrine Organs and Diseases (incl. Diabetes)
dc.titleS100A8 chemotactic protein is abundantly increased, but only a minor contributor to LPS-induced, steroid resistant neutrophilic lung inflammation in vivo
dc.typeJournal Article
dc.identifier.doi10.1021/pr049829t
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMedicine - Royal Melbourne And Western Hospitals
melbourne.source.titleJOURNAL OF PROTEOME RESEARCH
melbourne.source.volume4
melbourne.source.issue1
melbourne.source.pages136-145
dc.research.coderfcd320305
dc.research.codeseo1998730105
melbourne.publicationid40597
melbourne.elementsid270874
melbourne.contributor.authorBozinovski, Steven
melbourne.contributor.authorCross, Maddalena
melbourne.contributor.authorVlahos, Ross
melbourne.contributor.authorJONES, JESSICA
melbourne.contributor.authorReynolds, Eric
melbourne.contributor.authorHamilton, John
melbourne.contributor.authorAnderson, Gary
dc.identifier.eissn1535-3907
melbourne.accessrightsThis item is currently not available from this repository


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