Pimecrolimus reduces eosinophil activation associated with calcium mobilization

Douglas A. Plager, Susan A. Henke, Yoshinori Matsuwaki, Arvind Madaan, Diane L. Squillace, Ross A. Dierkhising, Hirohito Kita

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: Pimecrolimus is a calcineurin inhibitor that inhibits T cell and mast cell activation and effectively treats atopic dermatitis. However, its effects on eosinophils, a cell type implicated in allergic disease pathology, are unknown. Therefore, we examined the effects of pimecrolimus on eosinophil superoxide anion production, degranulation and survival. Methods: Purified eosinophils from normal or atopic donors were incubated with serial dilutions of pimecrolimus (μM to nM) and then stimulated with platelet activating factor (PAF), interleukin 5 (IL5), secretory immunoglobulin A (sIgA) or Alternaria alternata (Alt) fungus extract. Eosinophil activation was monitored by cytochrome c reduction resulting from superoxide anion production and by a 2-site immunoassay for eosinophil-derived neurotoxin (EDN) in cellular supernatants, as a marker of degranulation. Eosinophil survival was measured by propidium iodide exclusion using flow cytometry after 4 days in culture. Results: Normal and atopic eosinophil superoxide anion production induced by PAF, and associated with increased intracellular calcium, was inhibited up to 37% with 1 μM pimecrolimus. However, superoxide anion production induced by IL5 and sIgA was not consistently inhibited. EDN release, which ultimately depends on calcium, was inhibited about 30% with PAF, IL5 and sIgA stimulation for normal and atopic donor eosinophils. Furthermore, calcium-dependent Alt-induced EDN release was inhibited up to 49% with nanomolar pimecrolimus. Finally, increased eosinophil survival promoted by IL5 and sIgA was not influenced by pimecrolimus. Conclusion: Pimecrolimus moderately inhibits eosinophil superoxide anion production and EDN release associated with calcium mobilization, which may contribute to its efficacy in treating atopic dermatitis.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalInternational archives of allergy and immunology
Volume149
Issue number2
DOIs
StatePublished - May 1 2009

Keywords

  • Alternaria alternate
  • Atopic dermatitis
  • Calcineurin inhibitor
  • Eosinophil
  • Fungus
  • Pimecrolimus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Plager, D. A., Henke, S. A., Matsuwaki, Y., Madaan, A., Squillace, D. L., Dierkhising, R. A., & Kita, H. (2009). Pimecrolimus reduces eosinophil activation associated with calcium mobilization. International archives of allergy and immunology, 149(2), 119-126. https://doi.org/10.1159/000189194