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The molecular basis of pulmonary surfactant – lessons from newborn infants

Jeffrey A Whitsett
Published in : HAMDAN MEDICAL JOURNAL ; Vol 5, No 3 (2012)
DOI : 10.7707/hmj.v5i3.180


Major scientific advances in prenatal and neonatal physiology have provided the basis for improved outcomes for preterm and other infants with disorders causing respiratory failure. Critical for the improved diagnosis and treatment of preterm infants was the recognition of the importance of the pulmonary surfactant system in the pathogenesis of respiratory distress syndrome in preterm infants. Dr Whitsett and colleagues in the Division of Neonatology, Perinatal and Pulmonary Biology, with many collaborators worldwide, have focused their attention on the molecular basis of lung formation, maturation and function for more than three decades. Initial questions regarding the regulation of surfactant synthesis and secretion in newborn infants led to the identification and study of the structure and function of the surfactant proteins (SP-A, SP-B, SP-C and SP-D) and the genes encoding them. The critical and distinct roles of each of the surfactant proteins in surfactant homeostasis and innate immunity were systematically explored and, in particular, their important role in surfactant replacement preparations used to treat newborn infants was elucidated. Reagents, including peptides, antibodies and transgenic mouse models, were developed for general use by the field of pulmonary biology for the study of common and idiopathic lung diseases. Molecular tools to add, mutate or delete genes selectively, in the respiratory epithelium of transgenic mice, enabled the development of models of human disease. Basic advances made in understanding the molecular basis of surfactant homeostasis, lung formation and function have provided the tools and strategies for the diagnosis and treatment of pulmonary diseases that were previously termed ‘idiopathic’.

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