title: CD11b(+) Mononuclear Cells Mitigate Hyperoxia-Induced Lung Injury in Neonatal Mice.
abstract: Bronchopulmonary dysplasia (BPD) is a common consequence of life-saving interventions for infants born with immature lungs. Resident tissue myeloid cells regulate lung pathology, but their role in BPD is poorly understood. To determine the role of lung interstitial myeloid cells in neonatal responses to lung injury, we exposed newborn mice to hyperoxia, a neonatal mouse lung injury model with features of human BPD. In newborn mice raised in normoxia, we identified a CD45(+) F4/80(+) CD11b(+), Ly6G(lo-int) CD71(+) population of cells in lungs of neonatal mice present in significantly greater percentages than in adult mice. In response to hyperoxia, surface marker and gene expression in whole lung macrophages/monocytes was biased to an alternatively activated phenotype. Partial depletion of these CD11b(+) mononuclear cells using CD11b-diphtheria toxin (DT) receptor transgenic mice resulted in 60% mortality by 40 hours of hyperoxia exposure with more severe lung injury, perivascular edema, and alveolar hemorrhage compared with DT-treated CD11b-DT receptor-negative controls, which displayed no mortality. These results identify an antiinflammatory population of CD11b(+) mononuclear cells that are protective in hyperoxia-induced neonatal lung injury in mice, and suggest that enhancing their beneficial functions may be a treatment strategy in infants at risk for BPD.
authors.affiliation: 1 Center for Lung Biology, and Department of Pediatrics, Divisions of.|2 Pulmonary Medicine and.
authors.forename: Laurie C
authors.initials: LC
authors.lastname: Eldredge
authors.affiliation: 3 Department of Comparative Medicine.|4 Department of Pathology.
authors.forename: Piper M
authors.initials: PM
authors.lastname: Treuting
authors.affiliation: 1 Center for Lung Biology, and Department of Pediatrics, Divisions of.|5 Department of Medicine, Division of Pulmonary and Critical Care Medicine.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Manicone
authors.affiliation: 6 Department of Immunology, University of Washington, Seattle, Washington; and.|7 Immunology Program, Benaroya Research Institute, Seattle, Washington.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.affiliation: 1 Center for Lung Biology, and Department of Pediatrics, Divisions of.|4 Department of Pathology.|5 Department of Medicine, Division of Pulmonary and Critical Care Medicine.
authors.forename: William C
authors.initials: WC
authors.lastname: Parks
authors.affiliation: 1 Center for Lung Biology, and Department of Pediatrics, Divisions of.|8 Critical Care Medicine.
authors.forename: John K
authors.initials: JK
authors.lastname: McGuire
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics / Q000378:metabolism; D018496:Hyperoxia / Q000150:complications*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D011654:Pulmonary Edema / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; D066257:Heparin-binding EGF-like Growth Factor; D018836:Inflammation Mediators
keywords: hyperoxia; interstitial macrophage; lung development; lung injury; macrophage polarization