Granulocyte Colony-Stimulating Factor, Granulocyte Macrophage Colony-Stimulating Factor and Neutrophils in the Bronchoalveolar Lavage Fluid of Premature Infants with Respiratory Distress Syndrome

Abstract

Background: Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) promote clonal maturation of neutrophil and macrophage progenitors and increase functional activities of mature cells. The number and activity of neutrophils and macrophages in the lung affect healing and remodeling following respiratory distress syndrome (RDS). Questions of the Study: (1) Are G-CSF and GM-CSF present in the airways of preterm neonates with RDS? (2) Do airway G-CSF and GM-CSF concentrations correlate with neutrophil and macrophage number in the bronchoalveolar lavage (BAL) fluid? (3) Are alveolar macrophages a source of airway G-CSF and GM-CSF? (4) Is in vitro expression of G-CSF and GM-CSF by airway macrophages modified by dexamethasone, endotoxin, or hyperoxia? Methods: Eighteen preterm neonates with RDS requiring mechanical ventilation within the first 24 h of life underwent BAL on days 1, 3, 6, 10, 12, 15, 20, and 28 if still intubated. BAL G-CSF and GM-CSF concentrations were measured by ELISA, and neutrophils and macrophages were counted. Alveolar macrophages were cultured, and G-CSF and GM-CSF expression measured in the presence and absence of dexamethasone, endotoxin, and hyperoxia. Results: G-CSF and GM-CSF were present in the BAL of intubated preterm neonates. In infants who did not develop chronic lung disease (CLD) (n = 5), G-CSF and GM-CSF concentrations were highest in the first days of life, falling thereafter, while in those who did develop CLD (n = 13) these concentrations increased over time. Neutrophil concentrations in BAL fluid followed a similar pattern. Macrophages from BAL were identified as a source of G-CSF and GM-CSF mRNA and protein. G-CSF and GM-CSF expression by these macrophages was increased by endotoxin, decreased by dexamethasone, and unchanged by hyperoxia. Conclusions: G-CSF and GM-CSF are present in neonatal BAL, and may contribute significantly to the accumulation of alveolar neutrophils.