TY - JOUR
T1 - Prostaglandin E2 and phagocytosis of inhaled particulate matter by airway macrophages in cystic fibrosis
AU - Liu, Norrice M.
AU - Miyashita, Lisa
AU - Sanak, Marek
AU - Barratt, Benjamin
AU - Grigg, Jonathan
PY - 2020
Y1 - 2020
N2 - 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-E2 (PGE2) is increased in CF, and PGE2 suppresses AM phagocytosis, we sought evidence for PGE2-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 PGE2, and sputum PGE2 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 PGE2 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 PGE2 (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). PGE2 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 PGE2-dependent manner. Conclusion: Increased PGE2 in the CF airway suppresses phagocytosis of inhaled PM by AM.
AB - 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-E2 (PGE2) is increased in CF, and PGE2 suppresses AM phagocytosis, we sought evidence for PGE2-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 PGE2, and sputum PGE2 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 PGE2 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 PGE2 (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). PGE2 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 PGE2-dependent manner. Conclusion: Increased PGE2 in the CF airway suppresses phagocytosis of inhaled PM by AM.
KW - Airway macrophage
KW - Particulate matter
KW - Phagocytosis
KW - Prostaglandin E2
UR - http://www.scopus.com/inward/record.url?scp=85097070743&partnerID=8YFLogxK
U2 - 10.1016/j.jcf.2020.11.010
DO - 10.1016/j.jcf.2020.11.010
M3 - Article
C2 - 33250436
AN - SCOPUS:85097070743
SN - 1569-1993
JO - Journal Of Cystic Fibrosis
JF - Journal Of Cystic Fibrosis
ER -
