Abstract
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.
Highlights
Inflammatory bowel diseases (IBD) are chronic relapsing and remitting inflammatory disorders of the gastrointestinal tract which affect an increasing number of patients especially in industrialized countries with current prevalence rates for Crohn’s disease (CD) and ulcerative colitis (UC) exceedingCells 2019, 8, 1328; doi:10.3390/cells8111328 www.mdpi.com/journal/cells200–250/100,000 [1,2]
Neutrophils are often the first immune cells recruited to the site of inflammation and play a key role in combatting microbial invasion [11]
Monitoring neutrophil trafficking to the site of inflammation would be helpful for understanding their contribution to the pathogenesis of disease and this would help to visualize and assess the anti-inflammatory effects of new drugs
Summary
Inflammatory bowel diseases (IBD) are chronic relapsing and remitting inflammatory disorders of the gastrointestinal tract which affect an increasing number of patients especially in industrialized countries with current prevalence rates for Crohn’s disease (CD) and ulcerative colitis (UC) exceedingCells 2019, 8, 1328; doi:10.3390/cells8111328 www.mdpi.com/journal/cells200–250/100,000 [1,2]. Inhibition of gut homing of immune cells is a promising therapeutic option. Neutrophils are often the first immune cells recruited to the site of inflammation and play a key role in combatting microbial invasion [11]. When these mechanisms become uncontrolled, extensive tissue damage and development of chronic disease might be the consequence. Monitoring neutrophil trafficking to the site of inflammation would be helpful for understanding their contribution to the pathogenesis of disease and this would help to visualize and assess the anti-inflammatory effects of new drugs
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