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IκB kinase activity drives fetal lung macrophage maturation along a non-M1/M2 paradigm.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Aug 01; Vol. 193 (3), pp. 1184-93. Date of Electronic Publication: 2014 Jun 30. - Publication Year :
- 2014
-
Abstract
- In preterm infants, exposure to inflammation increases the risk of bronchopulmonary dysplasia, a chronic, developmental lung disease. Although macrophages are the key cells that initiate lung inflammation, less is known about lung macrophage phenotype and maturation. We hypothesized that fetal lung macrophages mature into distinct subpopulations during mouse development, and that activation could influence macrophage maturation. Expression of the fetal macrophage markers CD68, CD86, CD206, Ym1, fibrinogen-like protein 2, and indolamine-2, 3-dioxygenase was developmentally regulated, with each marker having different temporal patterns. Flow cytometry analysis showed macrophages within the fetal lung were less diverse than the distinctly separate subpopulations in newborn and adult lungs. Similar to adult alveolar macrophages, fetal lung macrophages responded to the TLR4 agonist LPS and the alternative activation cytokines IL-4 and IL-13. Using a macrophage-specific constitutively active IκB Kinase transgenic model (IKFM), we demonstrated that macrophage activation increased proinflammatory gene expression and reduced the response of fetal lung macrophages to IL-4 and IL-13. Activation also increased fetal lung macrophage proliferation. Fetal IKFM lungs contained increased percentages of more mature, CD11b(low)F4/80(high) cells that also expressed higher levels of the alternative activation markers CD204 and CD206. Development of fetal lung macrophages into mature alveolar macrophages may therefore include features of both proinflammatory and alternative activation paradigms.<br /> (Copyright © 2014 by The American Association of Immunologists, Inc.)
- Subjects :
- Animals
Animals, Newborn
Biomarkers metabolism
Cell Differentiation genetics
Enzyme Activation immunology
Female
Gene Expression Regulation, Enzymologic immunology
Humans
I-kappa B Kinase physiology
Immunophenotyping
Inflammation enzymology
Inflammation immunology
Inflammation pathology
Lung Diseases enzymology
Lung Diseases immunology
Lung Diseases pathology
Macrophage Activation immunology
Macrophages, Alveolar enzymology
Macrophages, Alveolar pathology
Macrophages, Peritoneal enzymology
Macrophages, Peritoneal pathology
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Cell Differentiation immunology
Gene Expression Regulation, Developmental immunology
I-kappa B Kinase metabolism
Macrophages, Alveolar immunology
Macrophages, Peritoneal immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 193
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24981452
- Full Text :
- https://doi.org/10.4049/jimmunol.1302516