Pulmonary vascular endothelial growth factor-C in development and lung injury in preterm infants.
BACKGROUND
In mice, vascular endothelial growth factor-C (VEGF-C) plays an important role in development of the lymphatic system and in pathogenesis of pulmonary inflammation. Its role in development of the lymphatic system in human lung and in lung injury in newborns remains unclear.


OBJECTIVE
We studied the role of VEGF-C in developing human lung, and in acute and chronic lung injury in preterm infants.


METHODS
Included in the immunohistochemistry study were 10 fetuses, 15 control neonates without primary lung disease, 15 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia. Tracheal aspirate fluid samples of intubated very-low-birth-weight infants during Postnatal Weeks 1-5 were analyzed with ELISA.


RESULTS
Bronchiolar staining for VEGF-C was observed in all 48 samples. Alveolar epithelial staining was seen in most fetuses (8/10). In addition, staining was observed in alveolar macrophages in bronchopulmonary dysplasia (4/8), and late respiratory distress syndrome (2/7). VEGF receptor-3 (VEGFR-3) staining was observed in lymphatic endothelium adjacent to vascular endothelium. VEGF-C was expressed consistently in tracheal aspirate fluid, being highest during the first 2 postnatal days. Antenatal administration of glucocorticoids was associated with higher VEGF-C in tracheal aspirate fluid.


CONCLUSIONS
The pattern of pulmonary VEGF-C and VEGFR-3 protein expression and consistent VEGF-C protein appearance in tracheal aspirate fluid in human preterm infants indicate a role for VEGF-C in the physiologic development of the lymphatic system of the lung.
Janér
Joakim
J
Hospital for Children and Adolescents, Department of Surgery, Helsinki University Central Hospital, and Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, University of Helsinki, Helsinki, Finland. joakim.janer@helsinki.fi
Lassus
Patrik
P
Haglund
Caj
C
Paavonen
Karri
K
Alitalo
Kari
K
Andersson
Sture
S
D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D047109:Fetal Development; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism; D019102:Infant, Very Low Birth Weight / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D012044:Regression Analysis; D012127:Respiratory Distress Syndrome, Newborn / Q000209:etiology; D014132:Trachea / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000187:drug effects / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism*
D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3