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

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 n<smlcap>M</smlcap>) 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.

Vitamin D receptor and STAT6 interactome governs oesophageal epithelial barrier responses to IL-13 signalling

“…Indeed, there is a positive association between body mass index and atopy rates 48. Furthermore, VD may exert pleiotropic effects on various immune cells, including reducing eosinophil activation,49 which may have additive effects on the VD-mediated attenuation of inflammation in eosinophilic gastrointestinal disorders, prompting further investigation of tissue-specific and cell-specific responses to VD in patients with eosinophilic gastrointestinal disorders. We propose that the oesophagus is normally equipped with VD-mediated molecular machinery that allows it to successfully respond to the variety of antigenic and biophysical stimuli encountered as environmental triggers.…”

Vitamin D in Asthma

“…Long-term follow-up of these patients is eagerly awaited. Liu et al 2006-Handsottir et al 2010-Beard et al 2011-Fabri et al 2011-Ruiter et al 2015-Ethier et al 2016 M A N U S C R I P T A C C E P T E D Liu et al 2006-Fabri et al 2011-Lan et al 2014-Xystrakis et al 2006-Nanzer et al 2014-Chambers et al 2015 reduced pro-inflammatory cytokine production by neutrophils but with enhanced anti-bacterial activity -Takahashi et al 2002-Subramanian et al 2017 …”

Serum Vitamin D Is Inversely Associated with Blood Eosinophil Count Among Adults with Allergic Asthma

“… 4 At the level of eosinophils, VD reduces necrosis and, consequently, the secondary release of cytotoxic granules from eosinophils in tissues. 5 Eosinophils cultured in a VD-free medium exhibit spontaneous activation; in contrast, the levels of activation products are reduced in the presence of VD. 6 …”