Masterson, Joanne C. and McNamee, Eóin N. and Jedlicka, Paul and Fillon, Sophie A. and Ruybal, Joseph and Hosford, Lindsay and Rivera-Nieves, Jesus and Lee, James J. and Furuta, Glenn T.
(2011)
CCR3 Blockade Attenuates Eosinophilic Ileitis and
Associated Remodeling.
American Journal of Pathology, 179 (5).
pp. 2302-2314.
ISSN 0002-9440
Abstract
Intestinal remodeling and stricture formation is a complication of inflammatory bowel disease (IBD) that often requires surgical intervention. Although eosinophils are associated with mucosal remodeling in other
organs and are increased in IBD tissues, their role in
IBD-associated remodeling is unclear. Histological and
molecular features of ileitis and remodeling were assessed using immunohistochemical, histomorphometric, flow cytometric, and molecular analysis (real-time
RT-PCR) techniques in a murine model of chronic eosinophilic ileitis. Collagen protein was assessed by Sircol
assay. Using a spontaneous eosinophilic Crohn’s-like
mouse model SAMP1/SkuSlc, we demonstrate an association between ileitis progression and remodeling over
the course of 40 weeks. Mucosal and submucosal eosinophilia increased over the time course and correlated
with increased histological inflammatory indices. Ileitis
and remodeling increased over the 40 weeks, as did
expression of fibronectin. CCR3-specific antibody-mediated reduction of eosinophils resulted in significant decrease in goblet cell hyperplasia, muscularis propria
hypertrophy, villus blunting, and expression of inflammatory and remodeling genes, including fibronectin.
Cellularity of local mesenteric lymph nodes, including
T- and B-lymphocytes, was also significantly reduced.
Thus, eosinophils participate in intestinal remodeling, supporting eosinophils as a novel therapeutic
target.
| Item Type: |
Article
|
| Keywords: |
CCR3; Blockade; Eosinophilic Ileitis;
Associated Remodeling; |
| Academic Unit: |
Faculty of Science and Engineering > Biology |
| Item ID: |
12497 |
| Identification Number: |
https://doi.org/10.1016/j.ajpath.2011.07.039 |
| Depositing User: |
Joanne Masterson
|
| Date Deposited: |
27 Feb 2020 15:53 |
| Journal or Publication Title: |
American Journal of Pathology |
| Publisher: |
Elsevier |
| Refereed: |
Yes |
| URI: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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