PGE(2)-treated macrophages inhibit development of allergic lung inflammation in mice

Christina Draijer, Carian E. Boorsma, Catharina Reker-Smit, Eduard Post, Klaas Poelstra, Barbro N. Melgert*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

In healthy lungs, many macrophages are characterized by IL-10 production, and few are characterized by expression of IFN regulatory factor 5 (formerly M1) or YM1 and/or CD206 (formerly M2), whereas in asthma, this balance shifts toward few producing IL-10 and many expressing IFN regulatory factor 5 or YM1/CD206. In this study, we tested whether redressing the balance by reinstating IL-10 production could prevent house dust mite-induced allergic lung inflammation. PGE2 was found to be the best inducer of IL-10 in macrophages in vitro. Mice were then sensitized and challenged to house dust mites during a 2 wk protocol while treated with PGE2 in differentways. Lung inflammation was assessed 3 d after the last house dust mite challenge. House dust miteexposed mice treated with free PGE(2) had fewer infiltrating eosinophils in lungs and lower YM1 serum levels than vehicle-treated mice. Macrophage-specific delivery of PGE(2) did not affect lung inflammation. Adoptive transfer of PGE(2)-treated macrophages led to fewer infiltrating eosinophils, macrophages, (activated) CD4(+), and regulatory T lymphocytes in lungs. Our study shows that the redirection of macrophage polarization by using PGE(2) inhibits development of allergic lung inflammation. This beneficial effect of macrophage repolarization is a novel avenue to explore for therapeutic purposes.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalJournal of Leukocyte Biology
Volume100
Issue number1
DOIs
Publication statusPublished - Jul-2016
Externally publishedYes

Keywords

  • hematopoietic
  • embryonic
  • targeting
  • asthma
  • alveolar
  • RESIDENT ALVEOLAR MACROPHAGES
  • T-CELL PROLIFERATION
  • TISSUE MACROPHAGES
  • IL-10 PRODUCTION
  • MONOCYTES
  • RECEPTOR
  • ASTHMA
  • ACTIVATION
  • PGE(2)
  • HYPERRESPONSIVENESS

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