|Budget Amount *help
¥2,800,000 (Direct Cost : ¥2,800,000)
Fiscal Year 1999 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Lung surfactant, a mixture of lipids and apoproteins, is synthesized in alveolar type II cells and is essential substance for maintaining lung homeostasis. This research project has revealed followings. (1) Phosphatidylcholine, a major lipidcomponent of lung surfactant, is synthesized in endoplasmic reticulum, transported to and stored in lamellar bodies via the Golgi-independent pathway. In contrast, surfactant protein A, one of the four apoproteins, is synthesized in endoplasmic reticulum, transported to the Golgi and is glycosylated, and is constitutively secreted out of the cells. The secreted protein is endocytosed into alveolar type II cells and transported to lamellar bodies. (2) The research also identified and partially characterized an intracellular molecule of an approximately 110 kD molecular weight on a gel filtration chromatography, which induces surfactant exocytosis. (3) ADP-ribosylation of adenylate cyclase-associated heterotrimeic G protein by cholera toxin unexpectedly but strongly inhibits lung surfactant secretion. These results indicate that the postulated pathway of lung surfactant so far is wrong, and have brought new aspects of lung surfactant biology. (4) Furthermore, we have investigated effects of lung deflation and several agents on alveolar water clearance. Taken together, these findings will lead to better understanding of pathogenesis of acute respiratory failure and a novel therapeutic strategy.
These results were published in medical journals, presented in medical meetings, and submitted to medical books. Especially, these papers published in American medical journals counted totally 11.295 of Impact Factor (Journal Citation Report, ISI).