期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 100, 期 1, 页码 95-102出版社
WILEY
DOI: 10.1189/jlb.3MAB1115-505R
关键词
hematopoietic; embryonic; targeting; asthma; alveolar
资金
- Netherlands Asthma Foundation (BNM) [3.2.10.056]
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.
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