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dc.contributor.authorBoorsma, CE
dc.contributor.authorvan der Veen, TA
dc.contributor.authorPutri, KSS
dc.contributor.authorde Almeida, A
dc.contributor.authorDraijer, C
dc.contributor.authorMauad, T
dc.contributor.authorFejer, Gyorgy
dc.contributor.authorBrandsma, C-A
dc.contributor.authorvan den Berge, M
dc.contributor.authorBossé, Yohan
dc.contributor.authorSin, D
dc.contributor.authorHao, K
dc.contributor.authorReithmeier, A
dc.contributor.authorAndersson, G
dc.contributor.authorOlinga, P
dc.contributor.authorTimens, Wim
dc.contributor.authorCasini, A
dc.contributor.authorMelgert, Barbro
dc.date.accessioned2017-11-27T13:14:27Z
dc.date.available2017-11-27T13:14:27Z
dc.date.issued2017-10-03
dc.identifier.issn2045-2322
dc.identifier.issn2045-2322
dc.identifier.other12570
dc.identifier.urihttp://hdl.handle.net/10026.1/10278
dc.description.abstract

<jats:title>Abstract</jats:title><jats:p>The enzyme tartrate resistant acid phosphatase (TRAP, two isoforms 5a and 5b) is highly expressed in alveolar macrophages, but its function there is unclear and potent selective inhibitors of TRAP are required to assess functional aspects of the protein. We found higher TRAP activity/expression in lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma compared to controls and more TRAP activity in lungs of mice with experimental COPD or asthma. Stimuli related to asthma and/or COPD were tested for their capacity to induce TRAP. Receptor activator of NF-κb ligand (RANKL) and Xanthine/Xanthine Oxidase induced TRAP mRNA expression in mouse macrophages, but only RANKL also induced TRAP activity in mouse lung slices. Several Au(III) coordination compounds were tested for their ability to inhibit TRAP activity and [Au(4,4′-dimethoxy-2,2′-bipyridine)Cl<jats:sub>2</jats:sub>][PF<jats:sub>6</jats:sub>] (AubipyOMe) was found to be the most potent inhibitor of TRAP5a and 5b activity reported to date (IC50 1.3 and 1.8 μM respectively). AubipyOMe also inhibited TRAP activity in murine macrophage and human lung tissue extracts. In a functional assay with physiological TRAP substrate osteopontin, AubipyOMe inhibited mouse macrophage migration over osteopontin-coated membranes. In conclusion, higher TRAP expression/activity are associated with COPD and asthma and TRAP is involved in regulating macrophage migration.</jats:p>

dc.format.extent12570-
dc.format.mediumElectronic
dc.languageen
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.subjectAnimals
dc.subjectAsthma
dc.subjectCoordination Complexes
dc.subjectEnzyme Inhibitors
dc.subjectGene Expression Regulation
dc.subjectGold
dc.subjectHumans
dc.subjectMacrophages, Alveolar
dc.subjectMice
dc.subjectOsteopontin
dc.subjectPulmonary Disease, Chronic Obstructive
dc.subjectRANK Ligand
dc.subjectRNA, Messenger
dc.subjectTartrate-Resistant Acid Phosphatase
dc.subjectXanthine Oxidase
dc.titleA Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000412138800006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue1
plymouth.volume7
plymouth.publication-statusPublished online
plymouth.journalScientific Reports
dc.identifier.doi10.1038/s41598-017-12623-w
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
plymouth.organisational-group/Plymouth/Users by role/Researchers in ResearchFish submission
dc.publisher.placeEngland
dcterms.dateAccepted2017-09-13
dc.identifier.eissn2045-2322
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1038/s41598-017-12623-w
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-10-03
rioxxterms.typeJournal Article/Review


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