TY - JOUR T1 - Effect of diesel exhaust particles (DEP) on monocyte-derived macrophage (MDM) mediator release and phagocytosis in chronic obstructive pulmonary disease (COPD) JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P618 AU - Gurpreet Sehra AU - Peter Barnes AU - Duncan Rogers AU - Louise Donnelly Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P618.abstract N2 - DEP increase hospitalisation of patients with COPD. DEP comprise a carbon core with adsorbed compounds, including endotoxin. DEP deposit in the lungs, and are targets for macrophages. Macrophages drive COPD pathophysiology by releasing inflammatory mediators, potentially via mitogen-activated protein kinase (MAPK) pathways. We hypothesised that DEP stimulate macrophage mediator release via MAPK, and this is increased in COPD. MDM from non-smokers, smokers or COPD patients were treated with either DEP, standard reference material (SRM)-2975, SRM-1650b or inert beads (30, 11 and 0.2µm diameter, respectively) (1-100μg/ml) for 24h. CXCL8 release was analysed by ELISA, phagocytosis of fluorescent beads by fluorimetry, activation of MAPK by immunobloting, cell viability by MTT, and endotoxin levels by Limolas-amoebocyte lysate assay. DEP inhibited MDM phagocytosis of beads from all goups in a concentration-dependent manner, with 100μg/ml giving ∼60% inhibition (with ∼24% decrease in viability). DEP, but not SRMs or beads, stimulated CXCL8 release by MDM compared with non-stimulated controls (not due to the presence of endotoxin). MDM from non-smokers or COPD patients were twice as responsive to DEP than cells from smokers. DEP-treated MDM activated p38 and ERK 1/2 MAPK pathways, but not JNK. A p38 inhibitor (PF755616) suppressed DEP-treated MDM activation of p38 and CXCL8 release with no effect on viability. In conclusion, DEP, but not other particles, stimulated MDM chemokine release via p38 and ERK, suggesting that DEP composition drives this response and that p38 inhibition may have therapeutic potential in COPD. ER -