PDF(Pubmed)
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.
摘要：
肺巨噬细胞在健康和疾病中起着至关重要的作用。性二态性显着影响组织驻留巨噬细胞的表型和功能。导致支气管肺发育不良（BPD）性二态结局的主要机制尚未确定。我们检验了生物学性别在肺泡巨噬细胞的转录状态中起关键作用的假设。使用新生儿小鼠高氧诱导的肺损伤作为人BPD的相关模型。测量了新生儿高氧暴露（95％FiO2，PND1-5：囊状阶段）在损伤后和正常氧恢复期间对肺骨髓细胞的影响。对雄性和雌性新生鼠肺暴露的室内空气和高氧的肺泡巨噬细胞（AM）进行大量RNA测序。损伤后暴露于高氧的肺中的AMs明显耗尽，随后两性都恢复了。肺泡巨噬细胞的转录组受新生儿高氧暴露和性别作为生物学变量的影响。与DNA损伤和干扰素信号相关的通路在雌性AMs中呈正富集；与葡萄糖和碳水化合物代谢相关的代谢通路在雄性AMs中呈正富集。而氧化磷酸化是负富集的。这些途径与来自插管的男性和女性人类早产新生儿的单核细胞和气道巨噬细胞共享。
