FIGURE 3.

Schematic of the alveolus and pulmonary surfactant homeostasis in the context of cigarette smoke exposure and chronic obstructive pulmonary disease (COPD). Chronic cigarette smoke exposure has directly cytotoxic and oxidative effects in the lungs, leading to increased oxidative damage and stress. a) Surfactant phospholipid damage and increased cellular debris stimulate surfactant uptake and recycling by alveolar macrophages and type I epithelial cells, respectively. As long-term exposure overwhelms these systems, alveolar macrophages from smokers and COPD patients become lipid-laden, exhibit impaired phagocytic ability and secrete a plethora of pro-inflammatory cytokines, which rapidly lead to the rapid recruitment of neutrophils from the circulation. It has recently been shown that recruited neutrophils also internalise pulmonary surfactant. b) Another hallmark of COPD is susceptibility to recurrent viral and bacterial infection, further exacerbating the pulmonary inflammatory response and adding an additional phagocytic burden on alveolar macrophages and neutrophils. Furthermore, increased lung tissue damage and inflammation leads to pulmonary vascular leak, making circulating surfactant protein (SP)-A and D levels a good indicator of disease severity in these patients.