Alveolar macrophage carbon is associated with COPD severity.

BACKGROUND: COPD is driven by the inhalation of noxious particles. A significant component of particulate matter is carbon, which is taken up by alveolar macrophages. We compared alveolar macrophage carbon levels in COPD patients to smokers and assessed the relationship of carbon load with macrophage size and phenotype. METHODS: Lung tissue from COPD patients (n=28) and smokers (n=15) was stained for alveolar macrophages. The area of carbon deposits within macrophages and macrophage size were measured. The effect of carbon exposure on macrophage size, phenotype marker expression (real-time PCR) and pro-inflammatory cytokine production (tumour necrosis factor-α (TNF-α) and CXCL8 by ELISA) was assessed in vitro using monocyte-derived macrophages (MDMs) from healthy donors. RESULTS: Carbon area (µm(2)) and percentage carbon area were significantly increased in COPD compared to smokers (5.0 µm(2) versus 1.3 µm(2), p=0.04; 4.2% versus 0.74%, p=0.04). Carbon area and percentage carbon area were negatively correlated with forced expiratory volume in 1†s % (r=†-0.43, p=0.001 and r=†-0.49, p=0.004, respectively). Alveolar macrophages containing carbon were significantly larger than carbon negative macrophages (16.1†µm versus 14.2†µm, p<0.0001, respectively). MDMs treated in vitro with carbon were significantly larger (19% at 62†µg·mL(-1)) than controls and had significantly increased expression of macrophage phenotype markers CD206, CD80 and CD38 and released greater levels of TNF-α and CXCL8. CONCLUSIONS: Alveolar macrophage carbon was increased in COPD patients compared to smokers and negatively correlated with lung function. Carbon skews macrophages to a phenotype of increased size and differential expression of macrophage phenotype genes. Alveolar macrophage carbon exposure may be a significant driver of macrophage dysfunction in COPD.