Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis
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 assess...
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2019-10-01
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author | Tobias M. Nowacki Philipp Lenz Dominik Bettenworth Markus Brückner Arne Bokemeyer Phil R. Tepasse Anne Helfen Moritz Wildgruber Michel Eisenblätter |
author_facet | Tobias M. Nowacki Philipp Lenz Dominik Bettenworth Markus Brückner Arne Bokemeyer Phil R. Tepasse Anne Helfen Moritz Wildgruber Michel Eisenblätter |
author_sort | Tobias M. Nowacki |
collection | DOAJ |
description | 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; <i>p</i> < 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. |
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spelling | doaj.art-6cf604e8147640c8b883af6c2fb948232023-09-02T19:46:55ZengMDPI AGCells2073-44092019-10-01811132810.3390/cells8111328cells8111328Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental ColitisTobias M. Nowacki0Philipp Lenz1Dominik Bettenworth2Markus Brückner3Arne Bokemeyer4Phil R. Tepasse5Anne Helfen6Moritz Wildgruber7Michel Eisenblätter8Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, D-48149 Münster, GermanyInstitute of Palliative Care, University of Münster, D-48149 Münster, GermanyDepartment of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, D-48149 Münster, GermanyDepartment of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, D-48149 Münster, GermanyDepartment of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, D-48149 Münster, GermanyDepartment of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, D-48149 Münster, GermanyTranslational Research Imaging Center, Department of Clinical Radiology, University Hospital Münster, D-48149 Münster, GermanyTranslational Research Imaging Center, Department of Clinical Radiology, University Hospital Münster, D-48149 Münster, GermanyTranslational Research Imaging Center, Department of Clinical Radiology, University Hospital Münster, D-48149 Münster, GermanyThe 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; <i>p</i> < 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.https://www.mdpi.com/2073-4409/8/11/1328in vivo imagingdiagnostic imagingexperimental colitisdextran sulfate sodium colitisinflammatory bowel diseasefluorescence imagingmurine endoscopy |
spellingShingle | Tobias M. Nowacki Philipp Lenz Dominik Bettenworth Markus Brückner Arne Bokemeyer Phil R. Tepasse Anne Helfen Moritz Wildgruber Michel Eisenblätter Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis Cells in vivo imaging diagnostic imaging experimental colitis dextran sulfate sodium colitis inflammatory bowel disease fluorescence imaging murine endoscopy |
title | Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis |
title_full | Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis |
title_fullStr | Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis |
title_full_unstemmed | Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis |
title_short | Target-Specific Fluorescence-Mediated Tomography for Non-Invasive and Dynamic Assessment of Early Neutrophil Infiltration in Murine Experimental Colitis |
title_sort | target specific fluorescence mediated tomography for non invasive and dynamic assessment of early neutrophil infiltration in murine experimental colitis |
topic | in vivo imaging diagnostic imaging experimental colitis dextran sulfate sodium colitis inflammatory bowel disease fluorescence imaging murine endoscopy |
url | https://www.mdpi.com/2073-4409/8/11/1328 |
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