Neutrophil migration and phagocytosis in chronic obstructive pulmonary disease

COPD is a leading cause of morbidity and mortality. A wealth of data supports a role of the neutrophil in disease pathogenesis. Despite abundance of neutrophils in airway secretions, patients suffer recurrent respiratory infections and colonisation suggesting immune dysfunction. This thesis describes impaired migratory function of neutrophils from patients with COPD, but not Alpha-1 Anti-Trypsin Deficiency (AATD) where similar inflammation is present. This is a feature of all COPD disease phenotypes and may constitute an early disease alteration to cell function, or a factor that predisposes patients to disease development. Aberrant migration may result in increased collateral tissue damage and delayed neutrophil arrival at sites of infection. Defective neutrophil migration in COPD can be improved by selective inhibition of PI3Kinase-γ and –δ, which may offer a strategy to reduce bystander tissue damage and improve bacterial clearance. The intrinsic ability of neutrophils to carry out effective phagocytosis in COPD and AATD does not appear reduced. However, in some patients, impaired serum opsonisation of bacteria reduced effective bacterial clearance by phagocytosis. Defective opsonisation may therefore make patients more vulnerable to bacterial colonisation and infection, and associated disease progression