title: PGE2-treated macrophages inhibit development of allergic lung inflammation in mice.
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 different ways. Lung inflammation was assessed 3 d after the last house dust mite challenge. House dust mite-exposed mice treated with free PGE2 had fewer infiltrating eosinophils in lungs and lower YM1 serum levels than vehicle-treated mice. Macrophage-specific delivery of PGE2 did not affect lung inflammation. Adoptive transfer of PGE2-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 PGE2 inhibits development of allergic lung inflammation. This beneficial effect of macrophage repolarization is a novel avenue to explore for therapeutic purposes.
authors.affiliation: Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands and Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Christina
authors.initials: C
authors.lastname: Draijer
authors.affiliation: Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands and Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Carian E
authors.initials: CE
authors.lastname: Boorsma
authors.affiliation: Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands and.
authors.forename: Catharina
authors.initials: C
authors.lastname: Reker-Smit
authors.affiliation: Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands and.
authors.forename: Eduard
authors.initials: E
authors.lastname: Post
authors.affiliation: Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands and.
authors.forename: Klaas
authors.initials: K
authors.lastname: Poelstra
authors.affiliation: Department of Pharmacokinetics, Toxicology, and Targeting, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands and Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, The Netherlands b.n.melgert@rug.nl.
authors.forename: Barbro N
authors.initials: BN
authors.lastname: Melgert
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology / Q000276:immunology*; D005260:Female; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D039981:Pyroglyphidae / Q000472:pathogenicity*
chemical_list: D016753:Interleukin-10; D015232:Dinoprostone
keywords: alveolar; asthma; embryonic; hematopoietic; targeting