Use of bioluminescence imaging to track neutrophil migration and its inhibition in experimental colitis

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dc.contributor.authorMurphy, Carola T.
dc.contributor.authorMoloney, Gerard M.
dc.contributor.authorHall, Lindsay J.
dc.contributor.authorQuinlan, Aoife
dc.contributor.authorFaivre, Emilie
dc.contributor.authorCasey, Pat G.
dc.contributor.authorShanahan, Fergus
dc.contributor.authorMelgar, Silvia
dc.contributor.authorNally, Kenneth
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2012-07-24T15:30:38Z
dc.date.available2012-07-24T15:30:38Z
dc.date.issued2010-10
dc.date.updated2012-07-24T10:59:59Z
dc.description.abstractInflammatory bowel disease (IBD) is associated with neutrophil infiltration into the mucosa and crypt abscesses. The chemokine interleukin (IL)-8 [murine homologues (KC) and macrophage inflammatory protein (MIP)-2] and its receptor CXCR2 are required for neutrophil recruitment; thus, blocking this engagement is a potential therapeutic strategy. In the present study, we developed a preclinical model of neutrophil migration suitable for investigating the biology of and testing new drugs that target neutrophil trafficking. Peritoneal exudate neutrophils from transgenic beta-actin-luciferase mice were isolated 12 h after intraperitoneal injection with thioglycollate, and were assessed phenotypically and functionally. Exudate cells were injected intravenously into recipients with dextran sodium sulphate (DSS)-induced colitis followed by bioluminescence imaging of whole-body and ex vivo organs at 2, 4 and 16-22 h post-transfer. Anti-KC antibody or an isotype control were administered at 20 mu g/mouse 1 h before transfer, followed by whole-body and organ imaging 4 h post-transfer. The peritoneal exudate consisted of 80% neutrophils, 39% of which were CXCR2+. In vitro migration towards KC was inhibited by anti-KC. Ex vivo bioluminescent imaging showed that neutrophil trafficking into the colon of DSS recipients was inhibited by anti-KC 4 h post-cell transfer. In conclusion, this study describes a new approach for investigating neutrophil trafficking that can be used in preclinical studies to evaluate potential inhibitors of neutrophil recruitment.en
dc.description.sponsorshipScience Foundation Ireland (02/CE/B124); Science Foundation Ireland (07/CE/B1368)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMurphy, C. T., Moloney, G., Hall, L. J., Quinlan, A., Faivre, E., Casey, P., Shanahan, F., Melgar, S. and Nally, K. (2010) 'Use of bioluminescence imaging to track neutrophil migration and its inhibition in experimental colitis', Clinical & Experimental Immunology, 162(1), pp. 188-196. doi: 10.1111/j.1365-2249.2010.04234.xen
dc.identifier.doi10.1111/j.1365-2249.2010.04234.x
dc.identifier.endpage196en
dc.identifier.issn1365-2249
dc.identifier.issued1en
dc.identifier.journaltitleClinical and Experimental Immunologyen
dc.identifier.startpage188en
dc.identifier.urihttps://hdl.handle.net/10468/640
dc.identifier.volume162en
dc.language.isoenen
dc.publisherBlackwell Publishing Ltd.en
dc.rights© 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology. The definitive version is available at www.blackwell-synergy.comen
dc.subjectIn-vivoen
dc.subjectExpressionen
dc.subjectCXCR2en
dc.subjectMiceen
dc.subjectGranulocytesen
dc.subjectNeutrophil recruitmenten
dc.subjectChemokinesen
dc.subject.lcshInflammatory bowel diseasesen
dc.subject.lcshUlcerative colitisen
dc.subject.lcshCrohn’s diseaseen
dc.titleUse of bioluminescence imaging to track neutrophil migration and its inhibition in experimental colitisen
dc.typeArticle (peer-reviewed)en
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