Macrophage Phagocytosis in COPD
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.
Inclusion Criteria:

 Healthy non-smoking subjects:

 All normal volunteers will meet the following criteria:

 Age 21-75 years. No history of respiratory or allergic disease. Normal baseline spirometry
 as predicted for age, sex and height. Non-smokers. No history of upper respiratory tract
 infection in the preceding six weeks. Not taking regular medication

 COPD subjects:

 COPD is diagnosed according to American Thoracic Society, European Respiratory Society and
 British Thoracic Society guidelines by the doctors in Professor Barnes' COPD clinic.

 All COPD volunteers will meet the following criteria:

 Age between 35-75 years. A smoking history of at least 10 pack years. ( 1 pack year = 20
 cigarettes per day for 1 year) FEV1:FVC ratio of <0.7, post-bronchodilator FEV1 of <85%
 predicted, reversibility with inhaled beta2-agonist of <15% of predicted FEV1: all three
 criteria are required.

 Exclusion Criteria:

 Subjects will not included in this study if they meet any of the following exclusion
 criteria:

 Clinically significant findings in the medical history or on physical examination other
 than those of COPD in the COPD group.

 Pregnant women or mothers who are breastfeeding. Subjects who are unable to give informed
 consent.-