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Ketotifen induces primary necrosis of human eosinophils

Hasela, H; Malm-Erjefält, Monika LU ; Erjefält, Jonas LU ; Giembycz, MA; Zhang, XZ; Moilanen, E and Kankaanranta, H (2005) In Journal of Ocular Pharmacology and Therapeutics 21(4). p.318-327
Abstract
Eosinophils are considered essential in the pathogenesis of allergy. Reduced eosinophil apoptosis is considered to be a key element in the formation of eosinophilia in allergic conditions. Antihistamines are widely used in the treatment of allergic disorders, but their effects on eosinophil apoptosis are poorly understood. The histamine HI-receptor antagonist, ketotifen, is available orally and as eye drops for the treatment of allergic symptoms. The aim of our study was to investigate the possible effect of ketotifen on constitutive eosinophil apoptosis and on interleukin (IL)-5-mediated eosinophil survival. Isolated peripheral blood eosinophils were cultured with or without the survival-prolonging cytokine IL-5 and ketotifen. Apoptosis... (More)
Eosinophils are considered essential in the pathogenesis of allergy. Reduced eosinophil apoptosis is considered to be a key element in the formation of eosinophilia in allergic conditions. Antihistamines are widely used in the treatment of allergic disorders, but their effects on eosinophil apoptosis are poorly understood. The histamine HI-receptor antagonist, ketotifen, is available orally and as eye drops for the treatment of allergic symptoms. The aim of our study was to investigate the possible effect of ketotifen on constitutive eosinophil apoptosis and on interleukin (IL)-5-mediated eosinophil survival. Isolated peripheral blood eosinophils were cultured with or without the survival-prolonging cytokine IL-5 and ketotifen. Apoptosis was assessed by measuring the relative DNA content and by morphological analysis. Ketotifen was found to reverse eosinophil survival induced by interleukin-5. However, the flow cytometry histogram of DNA in propidium iodide-stained cells was not typical to apoptosis. Morphological analysis of the eosinophils by bright-field microscopy suggested that the effect of ketotifen was due to the induction of primary necrosis rather than apoptosis. Histological assessment of eosinophil ultrastructure by transmission electron microscopy confirmed signs of advanced necrosis. In summary, our results suggest that at clinically relevant drug concentrations, ketotifen induces primary necrosis in IL-5-treated human eosinophils. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Ocular Pharmacology and Therapeutics
volume
21
issue
4
pages
318 - 327
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000231427600008
  • scopus:23944477977
ISSN
1080-7683
DOI
10.1089/jop.2005.21.318
language
English
LU publication?
yes
id
15e8b506-3c06-4485-8bc9-8fff7f872116 (old id 226244)
date added to LUP
2007-08-16 09:32:22
date last changed
2017-05-28 04:28:56
@article{15e8b506-3c06-4485-8bc9-8fff7f872116,
  abstract     = {Eosinophils are considered essential in the pathogenesis of allergy. Reduced eosinophil apoptosis is considered to be a key element in the formation of eosinophilia in allergic conditions. Antihistamines are widely used in the treatment of allergic disorders, but their effects on eosinophil apoptosis are poorly understood. The histamine HI-receptor antagonist, ketotifen, is available orally and as eye drops for the treatment of allergic symptoms. The aim of our study was to investigate the possible effect of ketotifen on constitutive eosinophil apoptosis and on interleukin (IL)-5-mediated eosinophil survival. Isolated peripheral blood eosinophils were cultured with or without the survival-prolonging cytokine IL-5 and ketotifen. Apoptosis was assessed by measuring the relative DNA content and by morphological analysis. Ketotifen was found to reverse eosinophil survival induced by interleukin-5. However, the flow cytometry histogram of DNA in propidium iodide-stained cells was not typical to apoptosis. Morphological analysis of the eosinophils by bright-field microscopy suggested that the effect of ketotifen was due to the induction of primary necrosis rather than apoptosis. Histological assessment of eosinophil ultrastructure by transmission electron microscopy confirmed signs of advanced necrosis. In summary, our results suggest that at clinically relevant drug concentrations, ketotifen induces primary necrosis in IL-5-treated human eosinophils.},
  author       = {Hasela, H and Malm-Erjefält, Monika and Erjefält, Jonas and Giembycz, MA and Zhang, XZ and Moilanen, E and Kankaanranta, H},
  issn         = {1080-7683},
  language     = {eng},
  number       = {4},
  pages        = {318--327},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Journal of Ocular Pharmacology and Therapeutics},
  title        = {Ketotifen induces primary necrosis of human eosinophils},
  url          = {http://dx.doi.org/10.1089/jop.2005.21.318},
  volume       = {21},
  year         = {2005},
}