What question did this study set out to answer?

The research aims to understand how biological sex influences the metabolic resilience of alveolar macrophages in response to hyperoxia.

March 26, 2026Open Access

Modulation of Alveolar Macrophages by Sex as a Biological Variable

Puntos clave

The research aims to understand how biological sex influences the metabolic resilience of alveolar macrophages in response to hyperoxia.
Characterized bioenergetic profiles of male and female murine alveolar macrophage cell lines.
Quantified oxygen consumption and extracellular acidification rates using Seahorse extracellular flux analysis.
Conducted experiment with exposure to hyperoxia over 48 hours.
Female alveolar macrophages exhibited higher basal and maximal respiration than male counterparts.
Upon hyperoxia exposure, female macrophages had reduced maximal oxygen consumption rate and spare respiratory capacity, unlike males who showed minimal change.
Neonatal macrophages from both sexes experienced mitochondrial function suppression under hyperoxia, with a more significant decline in males.

Resumen

Background: Alveolar macrophages (AMs) play a key role in the innate immune system and the pathogenesis of bronchopulmonary dysplasia (BPD), a condition with a significant sex bias. However, the influence of biological sex on AM immunometabolism remains poorly defined. Objective: We tested the hypothesis that female AMs would exhibit greater metabolic resilience (less impact on their mitochondrial function) compared to male AMs upon exposure to hyperoxia. Methods: We characterized bioenergetic profiles of male (MH-S) and female (AMJ2-C11) adult murine AM cell lines and primary neonatal AMs from C57BL/6 pups. Oxygen consumption (OCR) and extracellular acidification rates (ECAR) were quantified using Seahorse extracellular flux analysis at baseline and following 48 hours of hyperoxia (85% O2). Results: Adult female AMs displayed an elevated basal and maximal respiration compared to males. Upon exposure to hyperoxia, female AMs showed decreased maximal OCR and spare respiratory capacity. Conversely, male AMs showed little change in oxidative phosphorylation. Uniquely, neonatal AMs of both sexes show a suppression in their mitochondrial function upon exposure to hyperoxia, but the decline is more significant in the male macrophages. In addition, the neonatal female macrophages also showed a higher glycolytic reserve compared to their baseline in room air, upon exposure to hyperoxia. Conclusions: Biological sex and developmental stage are fundamental determinants of AM bioenergetics. These intrinsic sex-specific mechanisms may underlie differential susceptibility to neonatal lung injury, underscoring the necessity of sex-specific therapeutic strategies.

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