Disruption of the surfactant protein A receptor SP-R210L (CD245α/MYO18Aα) alters respiratory function and iron sequestration in alveolar macrophages of aged mice

Yau, E.; Umstead, T. M.; Abdulqadir, R.; Fino, K.; Guan, Z.; Hu, S.; Diangelo, S.; Hassan, K.; Bingaman, S.; Atkins, H. M.; Cooper, T. K.; Arnold, A. C.; Halstead, E. S.; Chroneos, Z. C.

doi:10.1101/2021.04.14.439860

bioRxiv · 10.1101/2021.04.14.439860

Disruption of the surfactant protein A receptor SP-R210L (CD245α/MYO18Aα) alters respiratory function and iron sequestration in alveolar macrophages of aged mice

Yau, E.·Umstead, T. M.·Abdulqadir, R.·Fino, K.·Guan, Z.·Hu, S.·Diangelo, S.·Hassan, K.·Bingaman, S.·Atkins, H. M.·Cooper, T. K.·Arnold, A. C.·Halstead, E. S.·Chroneos, Z. C.

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Abstract

Previous studies demonstrated that the host defense collectins, surfactant protein A and complement component 1q, modulate tissue-dependent macrophage activation, pathogen clearance, and regulatory macrophage functions through the receptor SP-R210, which consists of two isoforms SP-R210L and SP-R210S. These isoforms are encoded by alternatively spliced mRNAs of the Myo18a MYO18A gene in mice and humans. The present study in conditional transgenic mice revealed novel age-related functions of the SP-R210L isoform in modulating pulmonary mechanics, iron sequestration in alveolar macrophages (AMs), and life-long maintenance of the alveolar macrophage population. Our findings support the novel idea that SP-R210L-deficient AMs undergo bi-directional epigenetic adaptation that results in chronic dysregulation of broncho-alveolar function, immune homeostasis, and maintenance of oncotic balance at the airway-capillary interface. Disruption of SP-R210L increases the risk for development of severe interstitial lung disease during development and aging.

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Yau, E., Umstead, T. M., Abdulqadir, R., Fino, K., Guan, Z., Hu, S., Diangelo, S., Hassan, K., Bingaman, S., Atkins, H. M., Cooper, T. K., Arnold, A. C., Halstead, E. S., Chroneos, Z. C.. 2021-04-14. Disruption of the surfactant protein A receptor SP-R210L (CD245α/MYO18Aα) alters respiratory function and iron sequestration in alveolar macrophages of aged mice. https://doi.org/10.1101/2021.04.14.439860

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