1. Calcitriol Reduces Eosinophil Necrosis Which Leads to the Diminished Release of Cytotoxic Granules
- Author
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Caroline Ethier, Yingqi Yu, Lisa Cameron, Francis Davoine, and Paige Lacy
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Necrosis ,Calcitriol ,Cell Survival ,Immunology ,Inflammation ,macromolecular substances ,Cell Degranulation ,03 medical and health sciences ,hemic and lymphatic diseases ,Internal medicine ,polycyclic compounds ,medicine ,Vitamin D and neurology ,Immunology and Allergy ,Eosinophilia ,Humans ,Active metabolite ,Chemistry ,General Medicine ,Eosinophil ,Flow Cytometry ,respiratory tract diseases ,Eosinophils ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Apoptosis ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,Interleukin-5 ,medicine.drug - Abstract
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.
- Published
- 2016