Carbon in airway macrophages from children with asthma.

Background Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E-2 and D-2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. Methods AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (mu m(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE(2) and PGD(2) metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis. Results AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE(2) and D-2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE(2) 10(-6) M, but not PGD(2) 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE(2) 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). Conclusions Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE(2) may contribute to impaired AM phagocytic function in severe asthma.