Colony stimulating factors cannot correct defective phagocytosis in COPD lung tissue macrophages

Bacterial exacerbations account for half of all hospitalisations of COPD patients in the UK. <i>Haemophilus influenza</i> (HI) and <i>Streptococcus pneumoniae</i> (SP) are the most common species. Dysfunctional phagocytosis and altered macrophage (mΦ) phenotype may contribute to this. Monocyte-derived macrophages differentiated in GM-CSF (GM) compared to M-CSF (M) have decreased phagocytosis <i>in vitro</i>. This study assessed the phagocytic ability of mature mΦ isolated from non-smokers (NS=3), smokers (S=3) and COPD patients (COPD=4) and examined whether culture in GM or M drives plasticity and alters phagocytosis. Lung tissue mΦ (TmΦ) isolated from NS, S and COPD were cultured in media alone, GM or M for 6d and phagocytosis measured by flow cytometry. There was no difference in % live cells (&gt;90%) capable of phagocytosing either bacterial <i>spp</i> between subject groups or culture conditions. Median fluorescence intensity (MFI) measured the amount of bacteria phagocytosed. MFI for both HI and SP was higher in NS compared to S and COPD for all conditions (Fig 1). TmΦ from COPD patients have the capacity to phagocytose bacteria but do not take up as many as NS TmΦ. The phagocytic ability of COPD TmΦ was not altered by GM or M indicating a lack of plasticity. These data suggest that COPD TmΦ have an inherent phagocytic defect that cannot be corrected by cytokines thought to drive phenotype.