Molecular and cellular processing of lung surfactant1

Molecular and cellular processing of lung surfactant1,STEPHEN L. YOUNG,CAROLE R. MENDELSON

Molecular and cellular processing of lung surfactant1   (Citations: 95)
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Pulmonary surfactant, a complex material that lines the alveolar surface of the lung, is synthesized in the type II pneumocyte. Surfactant consists largely of phospholipids, of which phosphatidylcholine is by far the most abundant component, and is mainly responsible for surface activity. Surfactant also contains four unique pro- teins, surfactant protein (SP)-A, SP-B, SP-C, and SP-D, which are synthesized in a lung-specific manner. SP-A and SP-D are glycoproteins (Mras 30,000-40,000) whereas SP-B and SP-C are small (Mr as 5,000-18,000), extremely hydrophobic proteolipids released from large precursors by proteolysis. Synthesis of surfactant lipids and proteins is developmentally regulated in fetal lung and can be ac- celerated by glucocorticoids and other hormones. Devel- oping fetal lung in vivo and in organ culture has been used extensively to study regulation of surfactant synthe- sis and gene expression. Glucocorticoids stimulate the rate of fetal lung phosphatidylcholine biosynthesis and the activity of the rate-regulatory enzyme, choline- phosphate cytidylyltransferase (CYT). The hormone, however, does not increase the amount of CYT; there is evidence that the increase in activity is mediated by in- creased fatty biosynthesis due to enhanced expression of the fatty acid synthase gene. Glucocorticoids also regulate expression of the SP-A, SP-B, and SP-C genes in the late gestation fetal lung. Hormone response elements and other cis-acting regulatory elements have been identified in the 5-flanking regions of the SP-A, SP-B, and SP-C genes. Surfactant phospholipids are stored in lamellar bodies, secretory granules in the type H cell, and secreted by exocytosis. Lameliar bodies are also rich in SP-B and SP-C but there are conflicting data on the cellular distri- bution of SP-A. Secretion of SP-A may be constitutive and occur independently of lamellar bodies. Phospha- tidyicholine secretion is a regulated process, and in iso- lated type II cells it can be stimulated by physiological and other agents that act via at least three signal- transduction mechanisms. After secretion, surfactant is transformed into tubular myelin, and the lipid and pro- tein components are separated as the lipid is inserted into a monolayer at the air-liquid interface. The majority of surfactant is removed from the alveolar space by reuptake into the type II cell by mechanisms that may include receptor-mediated endocytosis. Some components of sur-
Published in 1994.
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