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Article: Shed syndecan-1 restricts neutrophil elastase from α1- antitrypsin in neutrophilic airway inflammation

TitleShed syndecan-1 restricts neutrophil elastase from α1- antitrypsin in neutrophilic airway inflammation
Authors
Keywordsα1-antitrypsin
Bronchiectasis
Heparin
Neutrophil elastase
Sputum
Issue Date2009
PublisherAmerican Thoracic Society. The Journal's web site is located at http://ajrcmb.atsjournals.org
Citation
American Journal of Respiratory Cell and Molecular Biology, 2009, v. 41 n. 5, p. 620-628 How to Cite?
AbstractPersistent proteolytic imbalance in chronic inflammatory diseases has been ascribed to neutrophil elastase (NE)/antielastase imbalance in wound fluids. In sputum sols of patients with bronchiectasis, we found unopposed NE activity, despite overwhelming excess of the physiological antielastase, α1-antitrypsin (α1-AT). Western blot analysis found NE in a supramolecular complex with shed ectodomains of syndecan (Syn)-1 in sputum sol samples and, as such, inhibition of NE activity was incomplete, even with addition of exogenous α1-AT. To confirm that NE binding to heparan sulfate (HS) components of Syn-1 limits the antielastase effect, recombinant human Syn-1 was recovered from stable Syn-1 transfectants of a human B-lymphoid cell line (ARH-77). Western ligand blot confirmed that NE bound to HS moieties and α1-AT to the core protein of the recombinant product. Inhibition of NE activity by standard additions of α1-AT was incomplete unless Syn-1 had been deglycanated by heparitinase treatment. Surface plasmon resonance analysis revealed that NE binding to HS (equilibrium dissociation constant, ∼14 nM) could be outcompeted by heparin variants. We conclude that the HS moiety of shed Syn-1 binds and restricts NE from inhibition by α1-AT.
Persistent Identifierhttp://hdl.handle.net/10722/147613
ISSN
2015 Impact Factor: 4.082
2015 SCImago Journal Rankings: 1.622
ISI Accession Number ID
Funding AgencyGrant Number
Innovation and Technology CommissionITS/127/07
HKSAR
Hong Kong Research Grants Council
Funding Information:

This work was supported by grants from the Innovation and Technology Commission (ITS/127/07), HKSAR, and The Hong Kong Research Grants Council.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChan, SCHen_HK
dc.contributor.authorLeung, VOYen_HK
dc.contributor.authorIp, MSMen_HK
dc.contributor.authorShum, DKYen_HK
dc.date.accessioned2012-05-29T06:04:58Z-
dc.date.available2012-05-29T06:04:58Z-
dc.date.issued2009en_HK
dc.identifier.citationAmerican Journal of Respiratory Cell and Molecular Biology, 2009, v. 41 n. 5, p. 620-628en_HK
dc.identifier.issn1044-1549en_HK
dc.identifier.urihttp://hdl.handle.net/10722/147613-
dc.description.abstractPersistent proteolytic imbalance in chronic inflammatory diseases has been ascribed to neutrophil elastase (NE)/antielastase imbalance in wound fluids. In sputum sols of patients with bronchiectasis, we found unopposed NE activity, despite overwhelming excess of the physiological antielastase, α1-antitrypsin (α1-AT). Western blot analysis found NE in a supramolecular complex with shed ectodomains of syndecan (Syn)-1 in sputum sol samples and, as such, inhibition of NE activity was incomplete, even with addition of exogenous α1-AT. To confirm that NE binding to heparan sulfate (HS) components of Syn-1 limits the antielastase effect, recombinant human Syn-1 was recovered from stable Syn-1 transfectants of a human B-lymphoid cell line (ARH-77). Western ligand blot confirmed that NE bound to HS moieties and α1-AT to the core protein of the recombinant product. Inhibition of NE activity by standard additions of α1-AT was incomplete unless Syn-1 had been deglycanated by heparitinase treatment. Surface plasmon resonance analysis revealed that NE binding to HS (equilibrium dissociation constant, ∼14 nM) could be outcompeted by heparin variants. We conclude that the HS moiety of shed Syn-1 binds and restricts NE from inhibition by α1-AT.en_HK
dc.languageengen_US
dc.publisherAmerican Thoracic Society. The Journal's web site is located at http://ajrcmb.atsjournals.orgen_HK
dc.relation.ispartofAmerican Journal of Respiratory Cell and Molecular Biologyen_HK
dc.subjectα1-antitrypsinen_HK
dc.subjectBronchiectasisen_HK
dc.subjectHeparinen_HK
dc.subjectNeutrophil elastaseen_HK
dc.subjectSputumen_HK
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshBronchiectasis - Enzymology - Immunology - Physiopathologyen_US
dc.subject.meshCell Lineen_US
dc.subject.meshChondroitin Sulfates - Metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshHeparitin Sulfate - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshLeukocyte Elastase - Metabolismen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshNeutrophils - Enzymologyen_US
dc.subject.meshPolysaccharide-Lyases - Metabolismen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshRecombinant Proteins - Metabolismen_US
dc.subject.meshRespiratory Function Testsen_US
dc.subject.meshSputum - Immunologyen_US
dc.subject.meshSurface Plasmon Resonanceen_US
dc.subject.meshSyndecan-1 - Genetics - Metabolismen_US
dc.subject.meshTransfectionen_US
dc.subject.meshAlpha 1-Antitrypsin - Metabolismen_US
dc.titleShed syndecan-1 restricts neutrophil elastase from α1- antitrypsin in neutrophilic airway inflammationen_HK
dc.typeArticleen_HK
dc.identifier.emailIp, MSM:msmip@hku.hken_HK
dc.identifier.emailShum, DKY:shumdkhk@hkucc.hku.hken_HK
dc.identifier.authorityIp, MSM=rp00347en_HK
dc.identifier.authorityShum, DKY=rp00321en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1165/rcmb.2008-0185OCen_HK
dc.identifier.pmid19251947-
dc.identifier.scopuseid_2-s2.0-70450159308en_HK
dc.identifier.hkuros163598-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70450159308&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume41en_HK
dc.identifier.issue5en_HK
dc.identifier.spage620en_HK
dc.identifier.epage628en_HK
dc.identifier.isiWOS:000271137700014-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectHeparan sulfate oligosaccharide preparations - novel therapeutics in chronic inflammation-
dc.identifier.scopusauthoridChan, SCH=35261745200en_HK
dc.identifier.scopusauthoridLeung, VOY=40261911000en_HK
dc.identifier.scopusauthoridIp, MSM=7102423259en_HK
dc.identifier.scopusauthoridShum, DKY=7004824447en_HK

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