CCR3 Blockade Attenuates Eosinophilic Ileitis and Associated Remodeling

Masterson, Joanne C.; McNamee, Eóin N.; Jedlicka, Paul; Fillon, Sophie; Ruybal, Joseph; Hosford, Lindsay; Rivera–Nieves, Jesús; Lee, James J.; Furuta, Glenn T.

doi:10.1016/j.ajpath.2011.07.039

Cited by 37 publications

(46 citation statements)

References 49 publications

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“…Dexamethasone treatments were performed as described21 (figure 2). See supplementary materials (available online only).…”

Section: Methodsmentioning

confidence: 99%

“…Tissues were fixed with 10% neutral buffered formalin and processed in preparation for being paraffin embedded 21. Serial sections from these paraffin tissue blocks were cut (5 μm) and were either stained with H&E or subjected to histological assessments (see table 1) or immunohistochemistry using either an anti-mouse eosinophil major basic protein (MBP)-specific rat monoclonal antibody,22 the Ki67 monoclonal antibody to assess cell proliferation 23.…”

Section: Methodsmentioning

confidence: 99%

“…Leucocytes from tissue sources including spleen, bone marrow, peripheral blood and oesophagus were isolated as previously described 21 23 24. See supplementary materials (available online only).…”

Section: Methodsmentioning

confidence: 99%

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Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis

Masterson

McNamee

Hosford

et al. 2012

Gut

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Objective Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition of the oesophagus with limited treatment options. No previous transgenic model has specifically targeted the oesophageal mucosa to induce oesophageal eosinophilia. Design We developed a mouse model that closely resembles EoE by utilising oxazolone haptenation in mice with transgenic overexpression of an eosinophil poietic and survival factor (interleukin (IL)-5) in resident squamous oesophageal epithelia. Results Overexpression of IL-5 in the healthy oesophagus was achieved in transgenic mice (L2-IL5) using the squamous epithelial promoter Epstein–Barr virus ED-L2. Oxazolone-challenged L2-IL5 mice developed dose-dependent pan-oesophageal eosinophilia, including eosinophil microabscess formation and degranulation as well as basal cell hyperplasia. Moreover, oesophagi expressed increased IL-13 and the eosinophil agonist chemokine eotaxin-1. Treatment of these mice with corticosteroids significantly reduced eosinophilia and epithelial inflammation. Conclusions L2-IL5 mice provide a novel experimental model that can potentially be used in preclinical testing of EoE-related therapeutics and mechanistic studies identifying pathogenetic features associated with mucosal eosinophilia.

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“…Dexamethasone treatments were performed as described21 (figure 2). See supplementary materials (available online only).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis

Masterson

McNamee

Hosford

et al. 2012

Gut

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“…Furthermore, as indicated above, granule proteins such as eosinophil cationic protein, Epx, and major basic protein released by activated eosinophils during inflammation can contribute to tissue damage (alter barrier function) and dysfunction (diarrhea with bleeding) 9, 10, 11, 12. Deficiency of eotaxin‐1, the eosinophil‐specific chemokine, or blockade of its receptor (CCR3) resulting in depletion of eosinophils has been shown to attenuate inflammation in experimental models of IBD,9, 28 thus supporting the overall importance of eosinophil involvement in EGID.…”

Section: Discussionmentioning

confidence: 99%

Assessment of eosinophils in gastrointestinal inflammatory disease of dogs

Baştan

Seelig

Day

et al. 2018

Veterinary Internal Medicne

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BackgroundAccurate identification of eosinophils in the gastrointestinal (GI) tract of dogs with eosinophilic GI disease (EGID) by histological evaluation is challenging. The currently used hematoxylin and eosin (H&E) staining method detects intact eosinophils but does not detect degranulated eosinophils, thus potentially underrepresenting the number of infiltrating eosinophils.ObjectiveTo develop a more sensitive method for identifying and quantifying both intact and degranulated eosinophils to diagnose EGID more accurately.MethodsEndoscopically obtained paraffin‐embedded intestinal biopsy specimens from dogs with GI signs were examined. The study groups were dogs with eosinophilic enteritis (EE), lymphoplasmacytic and mixed enteritis, and control dogs with GI signs but no histologic changes on tissue sections. Consecutive sections were immunolabeled with monoclonal antibodies (mAbs) against the eosinophil granule protein eosinophil peroxidase (Epx) and stained by H&E, respectively. The number of eosinophils was manually quantified and classified as intact or degranulated.ResultsThe number of intact eosinophils detected in Epx mAb‐labeled duodenal sections was significantly higher compared with that in H&E‐stained sections, with a similar relationship noted in the colon and stomach. The Epx mAb allowed the unique assessment of eosinophil degranulation. The number of intact and degranulated eosinophils was significantly higher in duodenal lamina propria of the EE and mixed group compared to the control group.ConclusionImmunohistochemical detection of Epx provides a more precise method to detect GI tract eosinophils compared to H&E staining and could be used as an alternative and reliable diagnostic tool for assessment of biopsy tissues from dogs with EGID.

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“…As IBD inflammation switches to Th cell-driven responses, the absence of IL-4 and potentially other Th2 cell-polarizing factors reduces the Th2 cell-type immune response and the role of eosinophils in active inflammation. This then provides an environment for them to contribute to wound healing and fibrosis as inflammation subsides (Masterson et al, 2011). The work by Griseri et al (2015), in this issue of Immunity, not only challenges the perception of eosinophils as spectators in chronic IBD inflammation, but goes someway to explaining the presence and activity of eosinophils in diseases with immunophenotypes not normally associated with Th2 cell responses.…”

mentioning

confidence: 93%