Show simple item record

dc.contributor.authorTanino, Y.
dc.contributor.authorCoombe, Deirdre
dc.contributor.authorGill, S.
dc.contributor.authorKett, Warren
dc.contributor.authorKajikawa, O.
dc.contributor.authorProudfoot, A.
dc.contributor.authorWells, T.
dc.contributor.authorParks, W.
dc.contributor.authorWight, T.
dc.contributor.authorMartin, T.
dc.contributor.authorFrevert, C.
dc.date.accessioned2017-01-30T15:16:28Z
dc.date.available2017-01-30T15:16:28Z
dc.date.created2010-03-29T20:04:27Z
dc.date.issued2010
dc.identifier.citationTanino, Yoshi and Coombe, Deirdre R. and Gill, Sean E. and Kett, Warren C. and Kajikawa, Osamu and Proudfoot, Amanda E.I. and Wells, Timothy N.C. and Parks, William C. and Wight, Thomas N. and Martin, Thomas R. and Frevert, Charles W. 2010. Kinetics of chemokine-glycosaminoglycan interactions control neutrophil migration into the airspaces of the lungs. Journal of Immunology. 184 (5): pp. 2677-2685.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/44788
dc.identifier.doi10.4049/jimmunol.0903274
dc.description.abstract

Chemokine–glycosaminoglycan (GAG) interactions are thought to result in the formation of tissue-bound chemokine gradients. We hypothesized that the binding of chemokines to GAGs would increase neutrophil migration toward CXC chemokines instilled into lungs of mice. To test this hypothesis we compared neutrophil migration toward recombinant human CXCL8 (rhCXCL8) and two mutant forms of CXCL8, which do not bind to heparin immobilized on a sensor chip. Unexpectedly, when instilled into the lungs of mice the CXCL8 mutants recruited more neutrophils than rhCXCL8. The CXCL8 mutants appeared in plasma at significantly higher concentrations and diffused more rapidly across an extracellular matrix in vitro. A comparison of the murine CXC chemokines, KC and MIP-2, revealed that KC was more effective in recruiting neutrophils into the lungs than MIP-2. KC appeared in plasma at significantly higher concentrations and diffused more rapidly across an extracellular matrix in vitro than MIP-2. In kinetic binding studies, KC, MIP-2, and rhCXCL8 bound heparin differently, with KC associating and dissociating more rapidly from immobilized heparin than the other chemokines. These data suggest that the kinetics of chemokine–GAG interactions contributes to chemokine function in tissues. In the lungs, it appears that chemokines, such as CXCL8 or MIP-2, which associate and disassociate slowly from GAGs, form gradients relatively slowly compared with chemokines that either bind GAGs poorly or interact with rapid kinetics. Thus, different types of chemokine gradients may form during an inflammatory response. This suggests a new model, whereby GAGs control the spatiotemporal formation of chemokine gradients and neutrophil migration in tissue.

dc.publisherAmerican Association of Immunologists
dc.subjectinflammation
dc.subjectChemokine
dc.subjectlungs
dc.subjectneutrophils
dc.subjectglycosaminoglycan
dc.titleKinetics of chemokine-glycosaminoglycan interactions control neutrophil migration into the airspaces of the lungs
dc.typeJournal Article
dcterms.source.volume184
dcterms.source.number5
dcterms.source.startPage2677
dcterms.source.endPage2685
dcterms.source.issn0022-1767
dcterms.source.titleJournal of Immunology
curtin.departmentMolecular Immunology / Bio Sciences
curtin.accessStatusOpen access
curtin.facultyFaculty of Health Sciences
curtin.facultySchool of Biomedical Sciences


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record