title: Mast cells and exosomes in hyperoxia-induced neonatal lung disease.
abstract: Chronic lung disease of prematurity (CLD) is a frequent sequela of premature birth and oxygen toxicity is a major associated risk factor. Impaired alveolarization, scarring, and inflammation are hallmarks of CLD. Mast cell hyperplasia is a feature of CLD but the role of mast cells in its pathogenesis is unknown. We hypothesized that mast cell hyperplasia is a consequence of neonatal hyperoxia and contributes to CLD. Additionally, mast cell products may have diagnostic and prognostic value in preterm infants predisposed to CLD. To model CLD, neonatal wild-type and mast cell-deficient mice were placed in an O2 chamber delivering hyperoxic gas mixture [inspired O2 fraction (FiO2 ) of 0.8] (HO) for 2 wk and then returned to room air (RA) for an additional 3 wk. Age-matched controls were kept in RA (FiO2 of 0.21). Lungs from HO mice had increased numbers of mast cells, alveolar simplification and enlargement, and increased lung compliance. Mast cell deficiency proved protective by preserving air space integrity and lung compliance. The mast cell mediators β-hexosaminidase (β-hex), histamine, and elastase increased in the bronchoalveolar lavage fluid of HO wild-type mice. Tracheal aspirate fluids (TAs) from oxygenated and mechanically ventilated preterm infants were analyzed for mast cell products. In TAs from infants with confirmed cases of CLD, β-hex was elevated over time and correlated with FiO2 Mast cell exosomes were also present in the TAs. Collectively, these data show that mast cells play a significant role in hyperoxia-induced lung injury and their products could serve as potential biomarkers in evolving CLD.
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York;
authors.forename: A
authors.initials: A
authors.lastname: Veerappan
authors.affiliation: Department of Pediatrics, Weill Cornell Medicine, New York, New York;
authors.forename: M
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York;
authors.forename: A R
authors.initials: AR
authors.lastname: Savage
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York;
authors.forename: M L
authors.initials: ML
authors.lastname: Silverman
authors.affiliation: Department of Pediatrics, Weill Cornell Medicine, New York, New York;
authors.forename: W S
authors.initials: WS
authors.lastname: Chan
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medicine, New York, New York; and.
authors.forename: B
authors.initials: B
authors.lastname: Sung
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York;
authors.forename: B
authors.initials: B
authors.lastname: Summers
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York;
authors.forename: K C
authors.initials: KC
authors.lastname: Montelione
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York;
authors.forename: P
authors.initials: P
authors.lastname: Benedict
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York;
authors.forename: B
authors.initials: B
authors.lastname: Groh
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: A G
authors.initials: AG
authors.lastname: Vicencio
authors.affiliation: Department of Pediatrics, Weill Cornell Medicine, New York, New York;
authors.forename: H
authors.initials: H
authors.lastname: Peinado
authors.affiliation: Department of Pediatrics, Weill Cornell Medicine, New York, New York; Department of Genetic Medicine, Weill Cornell Medicine, New York, New York; and.
authors.forename: S
authors.initials: S
authors.lastname: Worgall
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medicine, New York, New York; rbsilve@med.cornell.edu.
authors.forename: R B
authors.initials: RB
authors.lastname: Silver
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D018496:Hyperoxia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007231:Infant, Newborn; D008168:Lung / Q000276:immunology / Q000473:pathology; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D020543:Proteome / Q000378:metabolism; D014132:Trachea / Q000378:metabolism
chemical_list: D020543:Proteome
keywords: biomarkers; exosomes; hyperoxia; mast cells