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Role of sex as a biological variable in neonatal alveolar macrophages
Redox Biology ( IF 10.7 ) Pub Date : 2024-08-02 , DOI: 10.1016/j.redox.2024.103296
Connor Leek 1 , Abiud Cantu 1 , Shilpa Sonti 1 , Manuel Cantu Gutierrez 1 , Laurie Eldredge 2 , Eniko Sajti 3 , He N Xu 4 , Krithika Lingappan 1
Redox Biology ( IF 10.7 ) Pub Date : 2024-08-02 , DOI: 10.1016/j.redox.2024.103296
Connor Leek 1 , Abiud Cantu 1 , Shilpa Sonti 1 , Manuel Cantu Gutierrez 1 , Laurie Eldredge 2 , Eniko Sajti 3 , He N Xu 4 , Krithika Lingappan 1
Affiliation
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 % FiO, 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.
中文翻译:
性别作为新生儿肺泡巨噬细胞生物学变量的作用
肺巨噬细胞在健康和疾病中发挥着至关重要的作用。性别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)性别二态性结果的主要机制仍不清楚。我们使用新生鼠高氧诱导的肺损伤作为人类 BPD 的相关模型,检验了生物性别在肺泡巨噬细胞的转录状态中起着至关重要作用的假设。测量了新生儿高氧暴露(95% FiO,PND1-5:囊状阶段)对损伤后急性期和含氧量正常恢复期间肺骨髓细胞的影响。对雄性和雌性新生小鼠肺部暴露的室内空气和高氧环境中的肺泡巨噬细胞 (AM) 进行批量 RNA 测序。损伤后,暴露于高氧环境的肺部的 AM 会急剧减少,随后男女都会恢复。肺泡巨噬细胞的转录组受到新生儿高氧暴露和性别作为生物变量的影响。与 DNA 损伤和干扰素信号传导相关的通路在女性 AM 中呈正向富集。与葡萄糖和碳水化合物代谢相关的代谢途径在雄性 AM 中呈正富集,而氧化磷酸化则呈负富集。这些途径与来自插管男性和女性早产新生儿的单核细胞和气道巨噬细胞共享。
更新日期:2024-08-02
中文翻译:
性别作为新生儿肺泡巨噬细胞生物学变量的作用
肺巨噬细胞在健康和疾病中发挥着至关重要的作用。性别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)性别二态性结果的主要机制仍不清楚。我们使用新生鼠高氧诱导的肺损伤作为人类 BPD 的相关模型,检验了生物性别在肺泡巨噬细胞的转录状态中起着至关重要作用的假设。测量了新生儿高氧暴露(95% FiO,PND1-5:囊状阶段)对损伤后急性期和含氧量正常恢复期间肺骨髓细胞的影响。对雄性和雌性新生小鼠肺部暴露的室内空气和高氧环境中的肺泡巨噬细胞 (AM) 进行批量 RNA 测序。损伤后,暴露于高氧环境的肺部的 AM 会急剧减少,随后男女都会恢复。肺泡巨噬细胞的转录组受到新生儿高氧暴露和性别作为生物变量的影响。与 DNA 损伤和干扰素信号传导相关的通路在女性 AM 中呈正向富集。与葡萄糖和碳水化合物代谢相关的代谢途径在雄性 AM 中呈正富集,而氧化磷酸化则呈负富集。这些途径与来自插管男性和女性早产新生儿的单核细胞和气道巨噬细胞共享。