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dc.contributor.authorLudwig, A.
dc.contributor.authorBerkhout, Theo
dc.contributor.authorMoores, K.
dc.contributor.authorGroot, P.
dc.contributor.authorChapman, G.
dc.date.accessioned2014-01-15T17:30:34Z
dc.date.available2014-01-15T17:30:34Z
dc.date.issued2002-01-15
dc.identifier.citationLudwig , A , Berkhout , T , Moores , K , Groot , P & Chapman , G 2002 , ' Fractalkine is expressed by smooth muscle cells in response to IFN-gamma and TNF-alpha and is modulated by metalloproteinase activity ' , Journal of Immunology , vol. 168 , no. 2 , pp. 604-612 .
dc.identifier.issn0022-1767
dc.identifier.otherPURE: 1521617
dc.identifier.otherPURE UUID: c68e5a43-be14-49b6-a153-702fa171f0cb
dc.identifier.otherWOS: 000173193700010
dc.identifier.otherScopus: 0037080042
dc.identifier.urihttp://hdl.handle.net/2299/12548
dc.description.abstractFractalkine/CX3C-chemokine ligand 1 is expressed as a membrane-spanning adhesion molecule that can be cleaved from the cell surface to produce a soluble chemoattractant. Within the vasculature, fractalkine is known to be generated by endothelial cells, but to date there are no reports describing its expression by smooth muscle cells (SMC). In this study we demonstrate that IFN-gamma and TNF-alpha, but not IL-1beta, cooperate synergistically to induce fractalkine mRNA and protein expression In cultured aortic SMC. We also report the release of functional, soluble fractalkine from the membranes of stimulated SMC. This release is inhibited by the zinc metalloproteinase inhibitor batimastat, resulting in the accumulation of membrane-associated fractalkine on the SMC surface. Therefore, an SMC-derived metalloproteinase activity is involved in fractalkine shedding. While soluble fractalkine present in SMC-conditioned medium is capable of inducing calcium transients in cells expressing the fractalkine receptor (CX3CR1), blocking experiments using neutralizing Abs reveal that it can be inactivated without affecting the chemotactic activity of SMC-conditioned media on monocytes. However, membrane-bound fractalkine plays a major role in promoting adhesion of monocytic cells to activated SMC. This fractalkine-mediated adhesion is further enhanced in the presence of batimastat, indicating that shedding of fractalkine from the cell surface down-regulates the adhesive properties of SMC. Hence, during vascular inflammation, the synergistic induction of fractalkine by IFN-gamma and TNF-alpha together with its metalloproteinase-mediated cleavage may finely control the recruitment of monocytes to SMC within the blood vessel wall.en
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofJournal of Immunology
dc.subjectADHESION
dc.subjectIN-VITRO
dc.subjectRECEPTOR CX(3)CR1
dc.subjectIDENTIFICATION
dc.subjectMONOCYTE CHEMOTACTIC PROTEIN
dc.subjectDENDRITIC CELLS
dc.subjectCX3C CHEMOKINE
dc.subjectHUMAN ATHEROSCLEROTIC PLAQUES
dc.subjectMATRIX METALLOPROTEINASES
dc.subjectCHEMOATTRACTANT
dc.titleFractalkine is expressed by smooth muscle cells in response to IFN-gamma and TNF-alpha and is modulated by metalloproteinase activityen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionDepartment of Pharmacy
dc.contributor.institutionMedicinal and Analytical Chemistry
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dcterms.dateAccepted2002-01-15
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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