Biomedicine

Before the First Breath

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Science  09 Apr 2004:
Vol. 304, Issue 5668, pp. 175
DOI: 10.1126/science.304.5668.175a

Childbirth begins with the onset of uterine contractions, but the signals that initiate this event have not been clearly identified. Maturation of the fetal lung is completed just before term. Alveolar cells in the lung secrete surfactant, a mixture of lipids and proteins that reduces surface tension and prevents the lungs from collapsing during normal breathing. Condon et al. observed the presence of surfactant protein A (SP-A) from the fetal mouse lung in the amniotic fluid (AF) late in gestation. This correlated with migration of AF macrophages to the uterine wall, an inflammatory response associated with normal term labor in humans. SP-A treatment activated isolated macrophages, stimulating their production of proinflammatory cytokines, and injection of SP-A into the amniotic fluid induced delivery. Macrophage migration was associated with activation of the transcription factor nuclear factor-kappa B (NF-κB) in the uterine muscle, suggesting that SP-A triggers a signaling cascade in the uterine wall that stimulates contraction, leading to parturition.

Many human infants that are born prematurely suffer from respiratory distress due to lack of lung surfactant. Shulenin et al. have identified inactivating mutations in a gene encoding a putative lipid transport protein in neonatal newborns with severe surfactant deficiency. The ATP-binding cassette transporter A3 (ABCA3) is located in intracellular lamellar bodies of alveolar type II cells where surfactant is produced, stored, and secreted. Other ABC proteins are known to function in lipid transport, and ABCA3 may transport lipids critical for lamellar body formation and surfactant metabolism. — LDC

Proc. Natl. Acad. Sci. U.S.A. 101, 4978 (2004); N. Engl. J. Med. 350, 1296 (2004).

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