Editors' ChoiceRespiratory Distress Syndrome

New Hope for Premature Newborns

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Science Translational Medicine  26 May 2010:
Vol. 2, Issue 33, pp. 33ec82
DOI: 10.1126/scitranslmed.3001292

Alveoli—spherical outcroppings in the lungs that are covered with a mesh of capillaries—are the sites where carbon dioxide in the blood is exchanged for oxygen. For efficient gas exchange, the surface tension at the interface between the alveolar surface and the air must be kept low. Pulmonary surfactant, which primarily consists of phosopholipids like phosphatidyl choline (PC), lines the alveolar walls, reduces the surface tension, and facilitates normal respiration. A deficiency of surfactant causes fatal respiratory distress syndrome, which is the primary cause of death in premature newborns. The biosynthesis of the surfactant phospholipids is not well understood, but two groups recently cloned the gene that encodes a lung lysophosphatidylcholine acyltransferase (LPCAT1) and demonstrated that this enzyme is involved in the synthesis of the form of PC found in surfactant, saturated PC. Now one of these groups, Bridges et al., confirm that LPCAT1 is an endoplasmic reticulum transmembrane protein of certain alveolar cells that is directly involved in surfactant synthesis. They found that mice bearing mutations in the Lpcat1 gene displayed increased perinatal mortality and respiratory distress. Lung tissue from these mice also had decreased LPCAT1 activity and reduced saturated PC content; the surfactant produced in these mice failed to reduce surface tension to the normal level. This study not only demonstrates the importance of the surfactant’s saturated PC content for a newborn’s transition to air breathing, but also defines that a threshold level of saturated PC is important for it to be effective. This finding could be relevant to humans; a recent clinical trial indicates that in extremely low–birth-weight infants, surfactant treatment was not effective, perhaps because the threshold level of saturated PC was not reached. LPCAT1 could provide an alternative treatment strategy for neonatal respiratory distress—as well as for acute lung injury caused by surfactant deficiency in adults.

J. P. Bridges et al., LPCAT1 regulates surfactant phospholipid synthesis and is required for transitioning to air breathing in mice. J. Clin. Invest. 120, 1736–1748 (2010). [Full Text]

SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Early CPAP versus surfactant in extremely preterm infants. N. Engl. J. Med. 16 May 2010 (10.1056/NEJMoa0911783). [Full Text]

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