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Open AccessArticle

Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis

1
Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, D-48149 Münster, Germany
2
Institute of Palliative Care, University of Münster, D-48149 Münster, Germany
3
Translational Research Imaging Center, Department of Clinical Radiology, University Hospital Münster, D-48149 Münster, Germany
4
Department of Diagnostic and Interventional Radiology, University Medical Center Freiburg, D-79106 Freiburg, Germany
*
Author to whom correspondence should be addressed.
Cells 2019, 8(11), 1328; https://doi.org/10.3390/cells8111328
Received: 2 September 2019 / Revised: 18 October 2019 / Accepted: 26 October 2019 / Published: 28 October 2019
The role of neutrophils in the pathogenesis of inflammatory bowel disease (IBD) is still only incompletely understood. Here, we evaluated target-specific fluorescence-mediated tomography (FMT) for visualization of neutrophil infiltration in murine experimental DSS-induced colitis. Colitis was assessed using clinical, endoscopic, and histopathological parameters. Intestinal neutrophil infiltration was determined at day 0, 4, and 10 by targeted FMT after injection of a neutrophil-specific fluorescence-labelled monoclonal antibody (Gr-1). Complementary, immunofluorescence tissue sections with Gr-1 and ELISA-based assessment of tissue myeloperoxidase (MPO) served as the gold standard for the quantification of neutrophil infiltration. Colitic animals showed decreasing body weight, presence of fecal occult blood, and endoscopic signs of inflammation. FMT revealed a significantly increased level of fluorescence only four days after colitis induction as compared to pre-experimental conditions (pmol tracer 73.2 ± 18.1 versus 738.6 ± 80.7; p < 0.05), while neither body weight nor endoscopic assessment showed significant changes at this early time. Confirmatory, post-mortem immunofluorescence studies and measurements of tissue MPO confirmed the presence of increased neutrophil infiltration in colitic mice compared to controls. Concluding, Gr-1 targeted FMT can detect early colonic infiltration of neutrophils in experimental colitis even before clinical symptoms or endoscopic alterations occur. Therefore, FMT might be an important tool for repetitive and non-invasive monitoring of inflammatory cell infiltrate in intestinal inflammation. View Full-Text
Keywords: in vivo imaging; diagnostic imaging; experimental colitis; dextran sulfate sodium colitis; inflammatory bowel disease; fluorescence imaging; murine endoscopy in vivo imaging; diagnostic imaging; experimental colitis; dextran sulfate sodium colitis; inflammatory bowel disease; fluorescence imaging; murine endoscopy
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Nowacki, T.M.; Lenz, P.; Bettenworth, D.; Brückner, M.; Bokemeyer, A.; Tepasse, P.R.; Helfen, A.; Wildgruber, M.; Eisenblätter, M. Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis. Cells 2019, 8, 1328.

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