P1.156: Disruption of the surfactant protein A receptor SP-R210L in alveolar macrophages alters perinatal alveolar formation and remodeling

Background: Macrophages have been implicated in lung branching morphogenesis and postnatal alveolar formation. Surfactant protein A (SP-A) produced by fetal alveolar type II epithelial cells in late gestation modulates inflammation that contributes to host defense and fetal-maternal communication at onset of parturition. The objective of this study is to elucidate the role that the alveolar macrophage SP-A receptor SP-R210L plays in perinatal lung development. We hypothesized that deletion of SP-R210L in AMs would disrupt perinatal alveolarization.

Methods: Conditional transgenic mice were generated by targeting exon 1 encoding the unique amino-terminal KE/PDZ domain of SP-R210L and selectively deleting SP-R210L in alveolar macrophages (AMs) via ItgaxCre-mediated inversion recombination. The impact of AM selective deletion of SP-R210L on perinatal lung development was studied by histological measurements on embryonic (E) E18.5 and postnatal (P) days P1, P7, and P14 in SP-R210L-deficient and littermate control mice. Lung tissue sections were stained by hematoxylin and eosin and the periodic acid-Schiff stain to evaluate alveolar morphology and differentiation of alveolar epithelial cells. Immunohistochemical staining with a polyclonal SP-A antibody was used to assess the impact of SP-R210L deletion on expression and localization of SP-A in the alveolar compartment.

Results: We show that conditional disruption of SP-R210L results in enlarged airspaces and deposition of SP-A, PAS-positive material, and cellular debris in alveolar spaces that are prominent in E18.5 and P1 lungs of SP-R210L-deficient mice. Alveolar simplification resembling bronchopulmonary dysplasia persisted in P7 and P14 lungs of SP-R210L-deficient mice.

Conclusion: Our findings support the novel idea that SP-R210L modulates lung remodeling, surfactant metabolism, and clearance of cellular debris by AMs in late gestation. Our study suggests that the SP-A/SP-R210L modulates perinatal alveolar development and long-term respiratory function.