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

• Published in: Scientific reports 2020-03, Vol.10 (1), p.4696-4696, Article 4696
• Main Authors: Zhang, Liang, Wallace, Craig D., Erickson, Jamie E., Nelson, Christine M., Gaudette, Stephanie M., Pohl, Calvin S., Karsen, Samuel D., Simler, Gricelda H., Peng, Ruoqi, Stedman, Christopher A., Laroux, F. Stephen, Wurbel, Marc A., Kamath, Rajesh V., McRae, Bradford L., Schwartz Sterman, Annette J., Mitra, Soumya
• Format: Article
• Language: English
• Subjects: 631/1647/245; 692/4020; Animal models; Animals; Biological Transport; Biomarkers; CD40 antigen; Colitis; Colon; Dextran; Dextran sulfate; Disease Models, Animal; Elastase; Fc receptors; Fluorescent indicators; Fusion protein; Humanities and Social Sciences; Immunohistochemistry; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - diagnosis; Inflammatory Bowel Diseases - etiology; Inflammatory Bowel Diseases - metabolism; Interleukin 22; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine; Leukocyte Elastase - metabolism; Mice; Microscopy, Confocal; Monoclonal antibodies; Mucosa; multidisciplinary; Neutrophils; Optical Imaging - methods; Permeability; Science; Science (multidisciplinary); Spectroscopy, Near-Infrared
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-61756-y

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.