Near infrared readouts offer sensitive and rapid assessments of intestinal permeability and disease severity in inflammatory bowel disease models

Autor: F. Stephen Laroux, Bradford L. McRae, Wallace Craig, Jamie Erickson, Stephanie M. Gaudette, Christopher Stedman, Christine M. Nelson, Gricelda H. Simler, Samuel D. Karsen, Annette J. Schwartz Sterman, Rajesh V. Kamath, Liang Zhang, Marc Wurbel, Soumya Mitra, Calvin S. Pohl, Ruoqi Peng
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Pathology
medicine.medical_specialty
medicine.drug_class
lcsh:Medicine
Inflammation
Monoclonal antibody
Inflammatory bowel disease
Article
Permeability
Imaging
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Animals
Intestinal Mucosa
lcsh:Science
Multidisciplinary
Intestinal permeability
Microscopy
Confocal
Spectroscopy
Near-Infrared
biology
business.industry
Optical Imaging
lcsh:R
Gastroenterology
Biological Transport
medicine.disease
Inflammatory Bowel Diseases
Fusion protein
Immunohistochemistry
Pathophysiology
digestive system diseases
Disease Models
Animal
030104 developmental biology
Permeability (electromagnetism)
Neutrophil elastase
biology.protein
030211 gastroenterology & hepatology
lcsh:Q
medicine.symptom
business
Leukocyte Elastase
Biomarkers
Zdroj: Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
Scientific Reports
ISSN: 2045-2322
Popis: Intestinal permeability and neutrophil activity are closely linked to inflammatory bowel disease (IBD) pathophysiology. Here we discuss two techniques for assessing permeability and neutrophil activity in mouse IBD models using near infrared (NIR) detection. To address the limitation of visible light readouts—namely high background—IRDye 800CW was used to enable rapid, non-terminal measurements of intestinal permeability. The increased sensitivity of NIR readouts for colon permeability is shown using dextran sulfate sodium (DSS) and anti-CD40 murine colitis models in response to interleukin-22 immunoglobulin Fc (IL22Fc) fusion protein and anti-p40 monoclonal antibody treatments, respectively. In addition to enhanced permeability, elevated levels of neutrophil elastase (NE) have been reported in inflamed colonic mucosal tissue. Activatable NIR fluorescent probes have been extensively used for disease activity evaluation in oncologic animal models, and we demonstrate their translatability using a NE-activatable reagent to evaluate inflammation in DSS mice. Confocal laser endomicroscopy (CLE) and tissue imaging allow visualization of spatial NE activity throughout diseased colon as well as changes in disease severity from IL22Fc treatment. Our findings with the 800CW dye and the NE probe highlight the ease of their implementation in preclinical IBD research.
Databáze: OpenAIRE
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