Macrophage Phagocytosis in COPD

Patients with chronic obstructive pulmonary disease (COPD) that have frequent chest infections are the patients most likely to become worse over time. Why these people are more susceptible to chest infections is not known. One reason might be that the white cells in their lungs called macrophages do not work properly. Normally, these cells remove all the debris inhaled into the lung. This can also include bacteria. In patients with COPD, these macrophages are not able to remove these particles. The research question addresses why this happens

Chronic obstructive pulmonary disease (COPD) comprises chronic bronchitis, small airways disease and emphysema. The major risk factor for the development of COPD is cigarette smoking therefore, the prevalence of this disease is increasing. COPD accounts for increasing numbers of hospital admissions due to increased numbers of chest infections and exacerbations. This may be related to the reduced capacity of macrophages from COPD patients to phagocytose bacteria and apoptotic cells. The reasons for this defect in the innate immune response in these subjects is unclear but there are suggestions that scavenger receptors may be altered by oxidative stress and reduce the phagocytotic pathway. This would be relevant in COPD, as increased oxidative stress is associated with cigarette smoking. We have preliminary data that shows a similar reduce phagocytotic response in monocyte-derived macrophages (MDM) from COPD patients compared with smokers and non-smokers. As these cells have not been exposed to oxidative stress other mechanisms may play a role in reducing phagocytosis. Using this MDM model, by taking blood from patients with COPD, we aim to investigate the mechanism of defective phagocytosis in COPD. We will measure the expression and regulation of cell surface scavenger receptors in cells of disease patients and control subjects and examine the signalling pathways leading to actin polymerization and phagosome formation. Finally, we aim to identify novel therapeutic strategies to reverse this effect and augment phagocytosis of macrophages in patients with COPD. Such a strategy would reduce chest infections and exacerbations and hence improve quality of life.