ABSTRACT
Infant respiratory distress syndrome (IRDS) can lead to impaired alveolarization and
dysmorphic vascularization of bronchopulmonary dysplasia. Clara cell secretory protein
(CC10) has anti-inflammatory properties but is deficient in the premature infant.
Because surfactant and vascular endothelial growth factor (VEGF) profiles are impaired
by inflammation and CC10 inhibits lung inflammation, we hypothesized that CC10 may
up-regulate surfactant protein (SP) and VEGF expression. Preterm lambs (n = 24; 126 ± 3 days [standard error] gestation) with IRDS were randomized to receive
100 mg/kg surfactant, 100 mg/kg surfactant followed by intratracheal 0.5, 1.5, or
5 mg/kg rhCC10 and studied for 4 hours. Gas exchange and lung mechanics were monitored;
surfactant protein and VEGF mRNA profiles in lung were assessed. There was a significant
rhCC10 dose-dependent increase in respiratory compliance and ventilation efficiency
index; both parameters were significantly greater in animals treated with 5 mg/kg
rhCC10 than those treated with surfactant alone. Similarly, there was a significant
rhCC10 dose and protein-dependent increase in surfactant protein (SP-B > SP-C > SP-A)
and dose- and isoform-dependent increase in VEGF (VEGF189 > VEGF165 > VEGF121). These
data demonstrate that early intervention with rhCC10 up-regulates surfactant protein
and VEGF expression, supporting the role of CC10 to protect against hyperoxia and
mechanical ventilation in the immature lung.
KEYWORDS
Clara cell secretory protein (CC10) - respiratory distress syndrome - mechanical ventilation
- hyperoxia - surfactant protein expression - VEGF isoform expression - lung inflammation
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Marla R WolfsonPh.D.
Department of Physiology, Temple University School of Medicine
3420 N. Broad Street, Philadelphia, PA 19140
eMail: marla.wolfson@temple.edu