The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

American Journal of Physiology. Lung Cellular and Molecular Physiology
Lars KnudsenAndrew J Gow

Abstract

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd(-/-)) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd(-/-) mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd(-/-) mice. These changes were reduced in DiNOS, and compared with Sftpd(-/-) mice a decrease in vol...Continue Reading

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Citations

Sep 25, 2016·European Journal of Radiology·Delphine L ChenEdwin J R van Beek
Dec 17, 2016·Cell and Tissue Research·Lars KnudsenMatthias Ochs
Aug 16, 2017·Veterinary Pathology·David K MeyerholzHeather A Flaherty
Feb 24, 2018·Frontiers in Medicine·Grith L Sorensen
Apr 30, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Lilian SteffenElena Lopez-Rodriguez
May 22, 2019·International Journal of Molecular Sciences·Julia HollenbachJulia Schipke
Aug 15, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Chang-Jiang GuoAndrew J Gow
Feb 6, 2020·International Journal of Molecular Sciences·Chiara GiraudoMassimiliano Casali
Oct 20, 2020·Frontiers in Physiology·Karolin AlbertLars Knudsen

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