PGE2‐treated macrophages inhibit development of allergic lung inflammation in mice

Redirecting macrophage polarization with PGE2 inhibits development of allergic lung inflammation, and independent of macrophage origin, increasing its potential for therapy. In healthy lungs, many macrophages are characterized by IL‐10 production, and few are characterized by expression of IFN regul...

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Published in:Journal of leukocyte biology 2016-07, Vol.100 (1), p.95-102
Main Authors: Draijer, Christina, Boorsma, Carian E., Reker‐Smit, Catharina, Post, Eduard, Poelstra, Klaas, Melgert, Barbro N.
Format: Article
Language:English
Subjects:
alveolar
Animals
asthma
Asthma - etiology
Asthma - metabolism
Asthma - prevention & control
Cells, Cultured
Dermatophagoides pteronyssinus
Dinoprostone - metabolism
embryonic
Eosinophils - cytology
Eosinophils - immunology
Female
hematopoietic
Interleukin-10 - immunology
Interleukin-10 - metabolism
Macrophages - immunology
Mice
Mice, Inbred BALB C
Pneumonia - etiology
Pneumonia - metabolism
Pneumonia - prevention & control
Primary Research
Pyroglyphidae - pathogenicity
targeting
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Summary:Redirecting macrophage polarization with PGE2 inhibits development of allergic lung inflammation, and independent of macrophage origin, increasing its potential for therapy. 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.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.3MAB1115-505R