Electron microscopy elucidates eosinophil degranulation patterns in patients with eosinophilic esophagitis

Saffari, Hedieh; Hoffman, Laura H.; Peterson, Kathryn A.; Fang, John C.; Leiferman, Kristin M.; Pease, Leonard F.; Gleich, Gerald J.

doi:10.1016/j.jaci.2013.11.024

Cited by 95 publications

(86 citation statements)

References 22 publications

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“…Free extracellular eosinophil granules have been detected by hematoxylin-eosin staining, immunostaining for their cationic proteins, and/or ultrastructural studies in tissue from patients with diverse eosinophilic diseases, including allergic asthma, atopic dermatitis, nasal polyposis, and eosinophilic esophagitis (9,10,20,30,39). Recent in vitro studies demonstrated primary eosinophil lysis after stimulation by a Ca 2ϩ ionophore or Siglec-8 engagement on primed human eosinophils (18,38).…”

mentioning

confidence: 99%

Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils

Zhu

Hogan

Molkentin

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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mentioning

confidence: 99%

Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils

Zhu

Hogan

Molkentin

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Research by Kodama et al [32 ]failed to show apoptotic eosinophils in mouse tissues following allergic inflammation. Moreover, evidence suggests that cytolytic eosinophils and eosinophilic granules are more commonly found in the allergic airway mucosa and in eosinophil esophagitis [6,16]. In humans, allergen exposure causes mucosal eosinophilia, accompanied by eosinophil piecemeal degranulation, eosinophil cytolysis, and the deposition of granules [14].…”

Section: Discussionmentioning

confidence: 99%

“…Cytolysis, causing a release of intracellular components, is the characteristic result of necrotic death. Necrosis in eosinophils seems to be a significant proinflammatory process in disease, since eosinophil cytolysis has often been observed in human [6,13,14,15,16] and animal [17] tissues undergoing eosinophilic inflammation. Therefore, we developed an interest in modulating eosinophil cell death to avoid eosinophilic cytotoxic mediator release with the goal of minimizing the presence of the proinflammatory components originating from these granulocytes within their surrounding environments.…”

Section: Introductionmentioning

confidence: 99%

Calcitriol Reduces Eosinophil Necrosis Which Leads to the Diminished Release of Cytotoxic Granules

Ethier

Yang

Cameron

et al. 2016

Int Arch Allergy Immunol

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Background: Asthma severity and eosinophilia correlate with a deficiency in vitamin D and its active metabolite calcitriol. Calcitriol modulates numerous leukocyte functions, but its effect on eosinophils is not fully understood. We postulated that calcitriol exerts a direct effect on eosinophil biology by modulating cell survival. Methods: Purified peripheral blood eosinophils from atopic donors were incubated in the presence of calcitriol for up to 14 days with or without IL-5. The effect of calcitriol on eosinophil viability was measured using the annexin-V/propidium iodide flow cytometry assay. We also examined the release of eosinophil peroxidase (EPX) in media using a flow cytometry assay with anti-EPX antibodies, and the enzymatic activity of EPX was measured by an OPD-based colorimetric assay. Results: We observed that calcitriol sustained cell viability in eosinophils with a concurrent reduction of necrotic cells. This effect was amplified by the addition of IL-5. In parallel, we observed that a physiological dose of calcitriol (10 nM) significantly reduced eosinophil necrosis and cytolytic release of EPX in media when coincubated with IL-5. Conclusion: These results suggest that calcitriol may exert a direct effect on eosinophils by reducing necrosis and the cytolytic release of inflammatory mediators like EPX.

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“…The study also advises that biopsies be taken in the proximal esophagus to distinguish from reflux esophagitis [62]. Newer histological scoring systems that take into account other inflammatory characteristics, such as eosinophil density, epithelial markers of inflammation such as dilated intracellular spaces, and fibrosis of the lamina propria may soon make diagnosis easier and treatment response more accurate [63]. One possibility that would explain why multiple biopsies are needed to reliably diagnose EoE may lie with the fact that eosinophils in EoE may not be able to be seen on H and E stains.…”

Section: Histologic Diagnosismentioning

confidence: 99%

Eosinophilic Esophagitis: A Comprehensive Review

Nt¹

2016

J Hepatol Gastroint Dis

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Eosinophilic Esophagitis (EoE) has been the subject of intense research and study over the past few years, as incidence and prevalence has increased in the United States, especially in adults. The signs, symptoms and complications of EoE arise from a complex interplay of genetic predisposition and environmental exposure that is not understood well at this time. The disease causes significant morbidity in both physical and psychological areas, and these effects may become permanent in some cases where remodeling of the epithelium is present. Treatment at this time mainly focuses on diet, medication and endoscopic dilation. While none of these entities can accomplish all of the treatment goals, careful selection of patients based on symptoms and physical findings can alleviate many of the complications of the disease. In addition, this review attempts to cull data from adult studies if possible, as much of the studies that involved children did not translate well to adult patients.

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Electron microscopy elucidates eosinophil degranulation patterns in patients with eosinophilic esophagitis

Cited by 95 publications

References 22 publications

Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils

Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils

Calcitriol Reduces Eosinophil Necrosis Which Leads to the Diminished Release of Cytotoxic Granules

Eosinophilic Esophagitis: A Comprehensive Review

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