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

Murphy, C. T., Moloney, G., Hall, L. J. ORCID:, 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 and Experimental Immunology, 162 (1). pp. 188-196. ISSN 1365-2249

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Inflammatory 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 β-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 µg/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.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User: Users 2731 not found.
Date Deposited: 08 Feb 2012 11:46
Last Modified: 20 Mar 2024 11:30
DOI: 10.1111/j.1365-2249.2010.04234.x

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