Age-related adaptation in airway, alveolar, and capillary micromechanics in SP-R210_L/MYO18Aα-deficient mice

Alternative splicing of MYO18A/Myo18A results in expression of several MYO18A protein isoforms classified as MYO18Aα-ε with different amino- and carboxy-terminal domains in mice and humans. The macrophage surfactant protein A receptor consists of SP-R210 L and SP-R210 S internal variants of MYO18Aα and β, respectively. Our recent communication reported that conditional deletion of MYO18Aα results in fetal lung hemorrhage and impairs survival of newborns after LPS-induced parturition in late gestation. Here, we report the effect of heritable transmission of conditional MYO18Aα disruption in lung function of young and aged mice. Histological and biochemical studies revealed hemosiderin iron deposition and increased ferritin levels in MYO18Aα-deficient alveolar macrophages (AMs) proportional to gene deletion zygosity, suggesting blood leakage to the alveolar space. Lack of MYO18Aα, however, did not compromise gas exchange, respiratory rate, intrathoracic pressure, or lung permeability to large solutes. Most parameters of blood and peripheral tissue integrity in MYO18Aα-deficient mice were normal except for mild microcytosis at 2-months of age, lower serum albumin concentration, lower heart rate in elderly mice, and increased fluid retention in the lungs following intracardiac perfusion with saline, suggesting oncotic pressure imbalance in lung vasculature. Accordingly, lack of MYO18Aα affected both vascular and airway compartments involving pulmonary vessel remodeling, macrophage activation and parenchymal inflammatory injury, incomplete dilation of pulmonary vessels after birth, and age-related adaptation of airway contractility and compliance. We report that MYO18Aα coordinates the micromechanics of bronchoalveolar and capillary lung compartments. Our findings support the concept that pulmonary surfactant contributes to mechanical stability of the alveolar-capillary barrier through the SP-A/MYO18Aα receptor pathway. Children's Miracle Network, PHS grant HL128746 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.