title: 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 nM) significantly reduced eosinophil necrosis and cytolytic release of EPX in media when coincubated with IL-5.
  
  
  CONCLUSIONS
  These results suggest that calcitriol may exert a direct effect on eosinophils by reducing necrosis and the cytolytic release of inflammatory mediators like EPX.
authors.affiliation: Pulmonary Research Group, University of Alberta, Edmonton, AB, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ethier
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Yu
authors.forename: Lisa
authors.initials: L
authors.lastname: Cameron
authors.forename: Paige
authors.initials: P
authors.lastname: Lacy
authors.forename: Francis
authors.initials: F
authors.lastname: Davoine
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology
chemical_list: D015848:Interleukin-5; D002117:Calcitriol