Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/5543
Citations
Scopus Web of Science® Altmetric
?
?
Full metadata record
DC FieldValueLanguage
dc.contributor.authorHaynes, D.en
dc.contributor.authorHarkin, D.en
dc.contributor.authorBignold, L.en
dc.contributor.authorHutchens, M.en
dc.contributor.authorTaylor, S.en
dc.contributor.authorFairlie, D.en
dc.date.issued2000en
dc.identifier.citationBiochemical Pharmacology, 2000; 60(5):729-733en
dc.identifier.issn0006-2952en
dc.identifier.issn1873-2968en
dc.identifier.urihttp://hdl.handle.net/2440/5543-
dc.description.abstractA cyclic peptide, Phe-[Orn-Pro-D-Cyclohexylalanine-Trp-Arg] (F-[OPdChaWR]), was recently shown in vitro to antagonise the binding of C5a to its receptor (CD88) on human polymorphonuclear leukocytes (PMNs) and in vivo to inhibit the neutropenia associated with septic shock induced by lipopolysaccharide (LPS) in rats. The aim of this study was to investigate whether F-[OPdChaWR] inhibits C5a-mediated chemotaxis of human PMNs using a modified Boyden chamber and C5a-stimulated release of cytokines from human monocytes in vitro. Approximately 50% of the chemotactic activity induced by 10 nM C5a was inhibited by 76 nM F-[OPdChaWR]. This correlated with inhibition of C5a-induced polarisation of PMNs by F-[OPdChaWR]. C5a alone failed to induce release of the inflammatory cytokines interleukin(IL)-1beta, tumour necrosis factor (TNF)-alpha, and IL-6 from human monocytes at concentrations up to 100 nM. However, in the presence of low concentrations of LPS (50 ng/mL), both IL-1beta and TNF-alpha were stimulated by 1 nM C5a. This co-stimulation was inhibited by F-[OPdChaWR] with IC(50)s of 0.8 and 6.9 nM for release of TNF-alpha and IL-1beta, respectively. No agonist activity was detected for F-[OPdChaWR] in either the chemotaxis or cytokine release assays at concentrations up to 50 microM. These results show that F-[OPdChaWR] inhibits several important inflammatory activities of C5a and suggest that C5a receptor antagonists may be effective in the treatment of inflammatory diseases mediated by C5a.en
dc.description.statementofresponsibilityDavid R. Haynes, Damien G. Harkin, Leon P. Bignold, Martin J. Hutchens, Stephen M. Taylor and David P. Fairlieen
dc.language.isoenen
dc.publisherPergamon-Elsevier Science Ltden
dc.rights© 2000 Elsevier Science Inc. All rights reserved.en
dc.subjectC5a; C5a antagonist; CD88 antagonist; chemotaxis; tumour necrosis factor-α; interleukin-1βen
dc.titleInhibition of C5a-induced neutrophil chemotaxis and macrophage cytokine production In vitro by a new C5a receptor antagonisten
dc.typeJournal articleen
dc.identifier.rmid0001000800en
dc.identifier.doi10.1016/S0006-2952(00)00361-0en
dc.identifier.pubid63576-
pubs.library.collectionPathology publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Pathology publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.