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NF‐kappaB activation in the fetal lung promotes macrophage maturation (715.3)
Author(s) -
Stouch Ashley,
Zaynagetdinov Rinat,
Barham Whitney,
Stinnett Amanda,
Yull Fiona,
Hoffman Hal,
Blackwell Timothy,
Prince Lawrence
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.715.3
Subject(s) - proinflammatory cytokine , macrophage , lung , immunology , integrin alpha m , fetus , bronchopulmonary dysplasia , inflammation , biology , alveolar macrophage , cd68 , tlr4 , medicine , flow cytometry , immunohistochemistry , in vitro , pregnancy , biochemistry , genetics , gestational age
In preterm infants, exposure to inflammation increases the risk of chronic, developmental lung disease bronchopulmonary dysplasia. While macrophages are the key cells that initiate lung inflammation, little 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 (FGL2), and indolamine‐2, 3‐dioxygenase (Ido1) was developmentally regulated. Flow cytometry analysis measured a narrow spectrum of CD11b expression in fetal lung macrophages, with separation into CD11b lo F4/80 hi and CD11b hi F4/80 lo subpopulations in newborn and adult lung. 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 IKKβeta 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. Fetal IKFM lungs contained increased percentages of more mature, CD11b lo F4/80 hi cells that also expressed higher levels of the alternative activation markers CD204 and CD206. The maturational programming of fetal lung macrophages into mature alveolar macrophages therefore did not follow traditional proinflammatory and alternative activation paradigms. Grant Funding Source : Supported by National Institutes of Health Grants HL097195, HL086324, HL116358, HL069765