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Role of sex as a biological variable in neonatal alveolar macrophages.
Leek, Connor; Cantu, Abiud; Sonti, Shilpa; Gutierrez, Manuel Cantu; Eldredge, Laurie; Sajti, Eniko; Xu, He N; Lingappan, Krithika.
Afiliación
  • Leek C; Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, PA, USA.
  • Cantu A; Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, PA, USA.
  • Sonti S; Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, PA, USA.
  • Gutierrez MC; Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, PA, USA.
  • Eldredge L; Department of Pediatrics, Division of Pediatric Pulmonology, University of Washington School of Medicine, Seattle Children's Hospital, WA, USA.
  • Sajti E; Department of Pediatrics, Division of Neonatology, University of California San Diego, San Diego, CA, USA.
  • Xu HN; Britton Chance Laboratory of Redox Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Lingappan K; Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, PA, USA. Electronic address: lingappank@chop.edu.
Redox Biol ; 75: 103296, 2024 09.
Article en En | MEDLINE | ID: mdl-39098263
ABSTRACT
The lung macrophages play a crucial role in health and disease. Sexual dimorphism significantly impacts the phenotype and function of tissue-resident macrophages. The primary mechanisms responsible for sexually dimorphic outcomes in bronchopulmonary dysplasia (BPD) remain unidentified. We tested the hypothesis that biological sex plays a crucial role in the transcriptional state of alveolar macrophages, using neonatal murine hyperoxia-induced lung injury as a relevant model for human BPD. The effects of neonatal hyperoxia exposure (95 % FiO2, PND1-5 saccular stage) on the lung myeloid cells acutely after injury and during normoxic recovery were measured. Alveolar macrophages (AM) from room air- and hyperoxia exposed from male and female neonatal murine lungs were subjected to bulk-RNA Sequencing. AMs are significantly depleted in the hyperoxia-exposed lung acutely after injury, with subsequent recovery in both sexes. The transcriptome of the alveolar macrophages is impacted by neonatal hyperoxia exposure and by sex as a biological variable. Pathways related to DNA damage and interferon-signaling were positively enriched in female AMs. Metabolic pathways related to glucose and carbohydrate metabolism were positively enriched in the male AMs, while oxidative phosphorylation was negatively enriched. These pathways were shared with monocytes and airway macrophages from intubated male and female human premature neonates.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Macrófagos Alveolares / Hiperoxia / Animales Recién Nacidos Límite: Animals / Female / Humans / Male / Newborn Idioma: En Revista: Redox Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Macrófagos Alveolares / Hiperoxia / Animales Recién Nacidos Límite: Animals / Female / Humans / Male / Newborn Idioma: En Revista: Redox Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos