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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Main Authors: Tobias M. Nowacki, Philipp Lenz, Dominik Bettenworth, Markus Brückner, Arne Bokemeyer, Phil R. Tepasse, Anne Helfen, Moritz Wildgruber, Michel Eisenblätter
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/8/11/1328
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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 &#177; 18.1 versus 738.6 &#177; 80.7; <i>p</i> &lt; 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 &#177; 18.1 versus 738.6 &#177; 80.7; <i>p</i> &lt; 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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