Neutrophils play a pivotal role in lung inflammation, but also clearance during and following inflammation. The role of neutrophils has been shown in a number of inflammatory lung diseases including ARDS, COPD, cystic fibroses, idiopathic pulmonary fibrosis, bronchiectasis and asthma . It appears that following a successful inflammatory response neutrophils can change from a pro-inflammatory to an anti-inflammatory phenotype. In this case, neutrophils stop producing and releasing pro-inflammatory mediators (i.e. leukotriene B4, platelet-activating factor, IL-8) and instead begin to release resolving mediators including bioactive lipids (i.e. lipoxins, resolvins) that enhance resolution following inflammation .
With age there are dramatic changes in neutrophil function, including reduced chemotaxis, phagocytosis and bactericidal mechanisms (fully reviewed in Chap. 1). The reduced bactericidal function will predispose to infection but the reduced che- motaxis also has consequences for lung tissue as this results in increased tissue bystander damage from neutrophil elastases released during migration . This reduced chemotactic behavior is due to dysregulated PI3 kinase intracellular signaling rather than reduced surface expression of chemoattractant receptors . Neutrophil granulocytes are acknowledged as key players of COPD, increased neutrophil lung populations are associated with tissue damage, increased inflammation and impaired tissue repair. There is recent evidence suggesting that neutrophil functions (migration, ROS generation, degranulation, phagocytosis) are also all impaired in COPD resulting in bias towards increased inflammation and reduced bacterial clearance .