The hypothesis examined in this thesis stated that macrophages from COPD subjects are defective in their ability to phagocytose. To investigate this hypothesis, engulfment by COPD macrophages was compared to that of cells from controls (smokers without COPD and non-smokers). Phagocytosis of polystyrene beads by monocytes-derived-macrophages (MDM) was comparable to that of alveolar macrophages, thus validating the MDM model. There was no difference in uptake of beads by any subject group, however, COPD MDM phagocytosed significantly less E. coli, H. influenzae and S. pneumoniae than cells from controls. This was not due to current medications as commonly prescribed therapies did not reduce phagocytosis of these bacteria. To identify the mechanism of this defeat, cytoskeletal arrangement was investigated. Actin polymerisation was not altered by disease, but COPD MDM had a greater susceptibility to microtubule disruptors and reduced levels of acetylated tubulin compared to control cells. Increasing microtubule acetylation enhanced uptake of H. influenzae, suggesting that this may be a novel mechanism for improving phagocytosis. Other mechanisms investigated included sphingosine-1-phosphate (S1P) signalling, as production of this molecule was increased by COPD MDM and inhibition of S1P signalling cascade increased uptake of H. influenzae. Microarray analysis demonstrated that following exposure to H. influenzae, COPD MDM expressed significantly more inflammatory genes than control cells, suggesting that these macrophages respond differently to bacteria. These findings suggest that COPD macrophages have a reduced phagocytic ability, which may result in bacterial colonisation, inflammation and exacerbations. Improving this macrophage function would offer therapeutic potential in this disease.