Lymphatic function is required prenatally for lung inflation at birth.

Abstract

Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants.

• Authors: Zoltán Jakus, Jason P Gleghorn, David R Enis, Aslihan Sen, Stephanie Chia, Xi Liu, David R Rawnsley, Yiqing Yang, Paul R Hess, Zhiying Zou, Jisheng Yang, Susan H Guttentag, Celeste M Nelson, Mark L Kahn
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 211 Issue 5 Pg. 815-26 (May 05 2014) ISSN: 1540-9538 [Electronic] United States
• PMID: 24733830 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• Ccbe1 protein, mouse
• DNA Primers
• Tumor Suppressor Proteins
• Vascular Endothelial Growth Factor Receptor-3

Topics

• Animals
• Animals, Newborn (physiology)
• Calcium-Binding Proteins (deficiency)
• DNA Primers (genetics)
• Echocardiography
• Embryo, Mammalian (physiology)
• Fetus (physiology)
• Immunohistochemistry
• Lung (physiology, ultrastructure)
• Lung Compliance (physiology)
• Lymphatic System (embryology, physiology)
• Lymphography
• Mice
• Mice, Knockout
• Microscopy, Electron, Transmission
• Pulmonary Edema (physiopathology)
• Real-Time Polymerase Chain Reaction
• Tumor Suppressor Proteins (deficiency)
• Vascular Endothelial Growth Factor Receptor-3 (metabolism)