Prostaglandin E and phagocytosis of inhaled particulate matter by airway macrophages in cystic fibrosis.

Background: Exposure to particulate matter (PM) air pollution is associated with adverse health outcomes in children with cystic fibrosis (CF). Airway macrophages (AM) phagocytose and retain inhaled PM in vivo, and the area of carbon in AM reflects both inhaled PM dose and phagocytic function. Since airway prostaglandin-E (PGE) is increased in CF, and PGE suppresses AM phagocytosis, we sought evidence for PGE-mediated suppression of AM phagocytosis of inhaled carbonaceous PM in CF.

Methods: After informed consent, urine was obtained from 20 controls and 24 CF children. In the subgroup of older children, at least one induced sputum was done in 20 controls and 19 CF children. Urinary tetranor PGEM, the major metabolite of PGE, and sputum PGE were measured by mass spectrometry. The area of carbon in AM was determined by image analysis. Exposure to PM was assessed by modelling and personal monitoring. The effect of either PGE or CF sputum supernatant on phagocytosis of diesel exhaust particle (DEP) by AM was assessed in vitro. Data were analysed by t-test.

Results: Both urinary tetranor PGEM (P<0.05), and sputum PGE (P<0.05) were increased in CF . Despite no difference in PM exposure between groups, the area of phagocytosed carbon by AM was decreased in children with CF (P<0.01). PGE suppressed phagocytosis of DEP by AM from both controls and CF (P<0.0001). CF sputum supernatant suppressed phagocytosis of DEP by AM (P<0.0001) in a PGE-dependent manner.

Conclusion: Increased PGE in the CF airway suppresses phagocytosis of inhaled PM by AM.