Lymphatic function is required prenatally for lung inflation at birth

Z. 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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)815-826
Number of pages12
JournalJournal of Experimental Medicine
Volume211
Issue number5
DOIs
Publication statusPublished - 2014

Fingerprint

Economic Inflation
Parturition
Lung
Lung Compliance
Respiratory Insufficiency
Pregnancy
Pulmonary Surfactants
Lymphatic Vessels
Surface Tension
Mechanics
Premature Infants
Surface-Active Agents
Lipoproteins
Blood Vessels
Mammals
Edema
Respiration
Embryonic Structures

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Jakus, Z., Gleghorn, J. P., Enis, D. R., Sen, A., Chia, S., Liu, X., ... Kahn, M. L. (2014). Lymphatic function is required prenatally for lung inflation at birth. Journal of Experimental Medicine, 211(5), 815-826. https://doi.org/10.1084/jem.20132308

Lymphatic function is required prenatally for lung inflation at birth. / Jakus, Z.; Gleghorn, Jason P.; Enis, David R.; Sen, Aslihan; Chia, Stephanie; Liu, Xi; Rawnsley, David R.; Yang, Yiqing; Hess, Paul R.; Zou, Zhiying; Yang, Jisheng; Guttentag, Susan H.; Nelson, Celeste M.; Kahn, Mark L.

In: Journal of Experimental Medicine, Vol. 211, No. 5, 2014, p. 815-826.

Research output: Contribution to journalArticle

Jakus, Z, Gleghorn, JP, Enis, DR, Sen, A, Chia, S, Liu, X, Rawnsley, DR, Yang, Y, Hess, PR, Zou, Z, Yang, J, Guttentag, SH, Nelson, CM & Kahn, ML 2014, 'Lymphatic function is required prenatally for lung inflation at birth', Journal of Experimental Medicine, vol. 211, no. 5, pp. 815-826. https://doi.org/10.1084/jem.20132308
Jakus, Z. ; Gleghorn, Jason P. ; Enis, David R. ; Sen, Aslihan ; Chia, Stephanie ; Liu, Xi ; Rawnsley, David R. ; Yang, Yiqing ; Hess, Paul R. ; Zou, Zhiying ; Yang, Jisheng ; Guttentag, Susan H. ; Nelson, Celeste M. ; Kahn, Mark L. / Lymphatic function is required prenatally for lung inflation at birth. In: Journal of Experimental Medicine. 2014 ; Vol. 211, No. 5. pp. 815-826.
@article{b8095ad1cc0a45b3ad20a777a41ff173,
title = "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.",
author = "Z. Jakus and Gleghorn, {Jason P.} and Enis, {David R.} and Aslihan Sen and Stephanie Chia and Xi Liu and Rawnsley, {David R.} and Yiqing Yang and Hess, {Paul R.} and Zhiying Zou and Jisheng Yang and Guttentag, {Susan H.} and Nelson, {Celeste M.} and Kahn, {Mark L.}",
year = "2014",
doi = "10.1084/jem.20132308",
language = "English",
volume = "211",
pages = "815--826",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - Lymphatic function is required prenatally for lung inflation at birth

AU - Jakus, Z.

AU - Gleghorn, Jason P.

AU - Enis, David R.

AU - Sen, Aslihan

AU - Chia, Stephanie

AU - Liu, Xi

AU - Rawnsley, David R.

AU - Yang, Yiqing

AU - Hess, Paul R.

AU - Zou, Zhiying

AU - Yang, Jisheng

AU - Guttentag, Susan H.

AU - Nelson, Celeste M.

AU - Kahn, Mark L.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84899732109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899732109&partnerID=8YFLogxK

U2 - 10.1084/jem.20132308

DO - 10.1084/jem.20132308

M3 - Article

C2 - 24733830

AN - SCOPUS:84899732109

VL - 211

SP - 815

EP - 826

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 5

ER -