Antenatal administration of granulocyte-macrophage colony-stimulating factor increases fetal lung maturation and endothelial nitric oxide synthase expression in the fetal rat lung.

ABSTRACT

OBJECTIVES: We investigated how maternal administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) induced fetal lung maturation compared with dexamethasone and whether maternal administration of GM-CSF and dexamethasone influenced the fetal lung eNOS expression. STUDY DESIGN: Thirty pregnant rats were divided into three groups of 10 rats each to receive GM-CSF, dexamethasone or saline solution at 16 days of gestation. Lung maturation using bronchial area and immunohistochemical lung airway epithelium and the vascular endothelial eNOS expression, using H Scores, were evaluated at 18 and 20 days of gestation. The statistical analysis was done with the Kruskal-Wallis test for comparisons of more than two groups and the Mann-Whitney U-test as a post hoc test using SPSS for windows release 10.0. Values of p>0, 0.05 were considered significant. RESULTS: On the 20th day of gestation both GM-CSF and dexamethasone injections caused a significant increase in fetal lung bronchial area, as compared with the controls (24.9%, 36.8%, 13.4%, respectively, p=0.001). eNOS immunoreactivity was observed in the endothelium of large pulmonary vessels and large and small airway epithelium on the 18th and 20th day of gestation. Maternal GM-CSF and dexamethasone increased lung eNOS expression in the airway epithelium when compared to controls. CONCLUSION: Maternal administration of GM-CSF induced fetal lung maturation and this effect may be mediated, at least partly, by an increase in the eNOS expression.