1. Near infrared readouts offer sensitive and rapid assessments of intestinal permeability and disease severity in inflammatory bowel disease models
- Author
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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, and Ruoqi Peng
- Subjects
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 - Abstract
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.
- Published
- 2020