Increased susceptibility of M2 monocyte-derived macrophages from COPD patients to oxidative stress

Chronic obstructive pulmonary disease (COPD) is associated with colonisation of the lower airways with bacteria including Haemophilus influenzae (HI) and Streptococcus pneumoniae (SP), and increased numbers of highly activated lung macrophages (mφ) with reduced phagocytic ability. Mφ may exist as M1-like (classically-activated, pro-inflammatory) or M2-like (alternatively-activated, anti-inflammatory) states. In COPD, M1 mφ may be more prevalent leading to pro-inflammatory conditions in the lung. To test this monocyte-derived mφ from non-smokers (NS), smokers (S) and COPD patients were cultured in GM-CSF (G-mφ, M1-like) or M-CSF (M-mφ, M2-like) for 12 days (n=3-6). Mφ were exposed to oxidative stress via treatment with 1-200 µM H 2 O 2 for 24 h after which phagocytosis of fluorescently labelled inert beads, or heat killed H.influenzae (HI) or S.pneumoniae (SP) was measured fluorimetrically. In all groups, M- mφ displayed higher phagocytic capacity than G- mφ (p In M-mφ from COPD patients, oxidative stress caused a concentration-dependent reduction in phagocytosis of HI (p M-mφ from COPD patients were more susceptible to oxidative stress than G-mφ which may contribute to their reduced presence in the lung. This abnormality in M-mφ should be further studied to elucidate the mechanisms behind this effect. Funded by COPDMAP.