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Re-Organization of Air Spaces in the Surfactant Protein C Aging Lung and Lipid Homeostasis
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A2327 - Re-Organization of Air Spaces in the Surfactant Protein C Aging Lung and Lipid Homeostasis
Author Block: E. Lopez-Rodriguez1, K. Sehlmeyer1, J. Ruwisch1, N. Roldan2, J. Perez-gil3, T. E. Weaver4, M. Ochs5, L. Knudsen6; 1Hannover Medical School, Hannover, Germany, 2Complutense University Madrid, Madrid, Spain, 3Biochemistry and Molecular Biology, Faculty of Biology - UCM, MADRID, Spain, 4Childrens Hosp Med Ctr, Cincinnati, OH, United States, 5Hannover Medical School, Institute of Functional and Applied Anatomy, Hannover D-30625, Germany, 6Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Lung surfactant is a complex mixture of lipids and proteins, which reduces surface tension at the air-water alveolar interface, decreasing the work of breathing and avoiding alveolar collapse. The main function of surfactant protein C (SP-C) is highlighted during compression of the interfacial film, where SP-C provides stability to the lipid film allowing lower surface tension. Moreover, SP-C has been described to counter-act cholesterol deleterious effect on surfactant film stability at the interface. Animal models with lack of SP-C breathe and live normally, but they show higher susceptibility to chronic lung diseases and induced fibrosis. A detailed structural analysis of the lung over 60 weeks of age showed an interesting re-organization of air-spaces in the SP-C deficient mice. Lack of SP-C increases the heterogeneity in alveolar volumes towards bigger over-distended alveolar spaces with age, leading to impaired alveolar dynamics compared to control animals. Numbers of cells in BAL are elevated in SP-C deficient mice and electron microscope pictures showed alveolar macrophages (AM) loaded with different vesicles and lamellar body (LB)-like structures. Therefore we studied the expression of lipid metabolism genes in these cells. To confirm whether SP-C may have an effect on lipid metabolism and degradation in AM, we performed in vitro endocytosis and gene expression studies using the murine alveolar macrophage cell line MH-S. Addition of cholesterol to surfactant lipids increased the endocytosis ratio of these cells and differentially regulates a set of genes involved in cholesterol transport, regulation and metabolism, such as Abca1, Abcg1, Npc2, Cd36, Pparg, Lal and Dhcr24. SP-C in combination with cholesterol in surfactant membranes further activates genes related to cholesterol transport and regulation. In conclusion, SP-C seems to play an important role not only in surfactant activity and alveolar dynamics, but also in lipid homeostasis in alveolar macrophages and the lung.
Author Block: E. Lopez-Rodriguez1, K. Sehlmeyer1, J. Ruwisch1, N. Roldan2, J. Perez-gil3, T. E. Weaver4, M. Ochs5, L. Knudsen6; 1Hannover Medical School, Hannover, Germany, 2Complutense University Madrid, Madrid, Spain, 3Biochemistry and Molecular Biology, Faculty of Biology - UCM, MADRID, Spain, 4Childrens Hosp Med Ctr, Cincinnati, OH, United States, 5Hannover Medical School, Institute of Functional and Applied Anatomy, Hannover D-30625, Germany, 6Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Lung surfactant is a complex mixture of lipids and proteins, which reduces surface tension at the air-water alveolar interface, decreasing the work of breathing and avoiding alveolar collapse. The main function of surfactant protein C (SP-C) is highlighted during compression of the interfacial film, where SP-C provides stability to the lipid film allowing lower surface tension. Moreover, SP-C has been described to counter-act cholesterol deleterious effect on surfactant film stability at the interface. Animal models with lack of SP-C breathe and live normally, but they show higher susceptibility to chronic lung diseases and induced fibrosis. A detailed structural analysis of the lung over 60 weeks of age showed an interesting re-organization of air-spaces in the SP-C deficient mice. Lack of SP-C increases the heterogeneity in alveolar volumes towards bigger over-distended alveolar spaces with age, leading to impaired alveolar dynamics compared to control animals. Numbers of cells in BAL are elevated in SP-C deficient mice and electron microscope pictures showed alveolar macrophages (AM) loaded with different vesicles and lamellar body (LB)-like structures. Therefore we studied the expression of lipid metabolism genes in these cells. To confirm whether SP-C may have an effect on lipid metabolism and degradation in AM, we performed in vitro endocytosis and gene expression studies using the murine alveolar macrophage cell line MH-S. Addition of cholesterol to surfactant lipids increased the endocytosis ratio of these cells and differentially regulates a set of genes involved in cholesterol transport, regulation and metabolism, such as Abca1, Abcg1, Npc2, Cd36, Pparg, Lal and Dhcr24. SP-C in combination with cholesterol in surfactant membranes further activates genes related to cholesterol transport and regulation. In conclusion, SP-C seems to play an important role not only in surfactant activity and alveolar dynamics, but also in lipid homeostasis in alveolar macrophages and the lung.
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