Use of bioluminescence imaging to track neutrophil migration and its inhibition in experimental colitis
2010
Murphy, C.T. | Moloney, G. | Hall, L.J. | Quinlan, A. | Faivre, E. | Casey, P. | Shanahan, F. | Melgar, S. | Nally, K.
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.
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