Published online December 11, 2006
PEDIATRICS Vol. 119 No. 1 January 2007, pp. e241-e246 (doi:10.1542/peds.2005-3039)
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ARTICLE

Pulmonary Endostatin Perinatally and in Lung Injury of the Newborn Infant

Joakim Janér, MDa, Sture Andersson, MD, PhDa, Caj Haglund, MD, PhDb and Patrik Lassus, MD, PhDa,c

a Hospital for Children and Adolescents
b Departments of Surgery
c Plastic Surgery, University of Helsinki, Helsinki, Finland

OBJECTIVE. Endostatin is a potent angiogenesis inhibitor. Angiogenesis is central for the development of the human lung. The role of endostatin in the development of the human lung and its connection to chronic lung disease remain unclear. We set out to study the role of endostatin in the developing human lung and in acute and chronic lung injury in the preterm infant.

METHODS. Nine fetuses, 14 control neonates without primary lung disease, 14 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia were included in the immunohistochemistry study. Tracheal aspirate-fluid samples of intubated very low birth weight infants during postnatal weeks 1 through 5 were analyzed with enzyme-linked immunosorbent assay.

RESULTS. Endothelial cell staining was positive for endostatin in all 45 samples. Staining of epithelial cells (cuboidal, bronchiolar, and alveolar) was seen mostly in fetuses, as well as in infants with late respiratory distress syndrome and bronchopulmonary dysplasia. Staining in alveolar macrophages was most abundant in infants with late respiratory distress syndrome and bronchopulmonary dysplasia. Endostatin was expressed consistently in tracheal aspirate fluid, being highest during the first postnatal day. Higher endostatin concentrations correlated with parameters reflecting lower lung maturity.

CONCLUSIONS. The pattern of pulmonary endostatin protein expression in immunohistochemistry and consistent endostatin protein appearance in tracheal aspirate fluid in human preterm infants indicate a role in the physiologic development of the lung. Preterm birth influences pulmonary endostatin protein expression, which may alter normal lung development and response to lung injury.

Key Words: lung development • endostatin • bronchopulmonary dysplasia • respiratory distress syndrome

Abbreviations: VLBW—very low birth weight • BPD—bronchopulmonary dysplasia • VEGF—vascular endothelial growth factor • GA—gestational age • Ig—immunoglobulin • SC—secretory component • FIO2—fraction of inspired oxygen • L/S—lecithin/sphingomyelin

Accepted Jul 7, 2006.


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