ABSTRACT

Reactive oxygen species (ROS) such as superoxide anion (O2 –) and the

hydroxyl radical (OH) are highly unstable species with unpaired electrons, capable of initiating oxidation. Biological systems are continuously exposed to oxidants, either generated endogenously by metabolic reactions (e.g., from mitochondrial electron transport during respiration or during activation of phagocytes) or exogenously, such as air pollutants or cigarette smoke. The lung exists in a high-oxygen environment and, together with its large surface area and blood supply, is susceptible to injury mediated by ROS. Production of ROS has been directly linked to oxidation of proteins, DNA, and lipids, which may cause direct lung injury or induce a variety of cellular responses, through the generation of secondary metabolic reactive species. ROS may alter remodeling of extracellular matrix and blood vessels, stimulate mucus secretion, inactivate antiproteases, cause apoptosis, and regulate cell proliferation (1,2) (Fig. 1). Alveolar repair responses and immune modulation in the lung may also be influenced by ROS. Furthermore, increased levels of ROS have been implicated in initiating inflammatory responses in the lungs through the activation of transcription factors such as nuclear factor-kappaB (NF-kB) and activator protein-1 (AP-1), signal transduction, chromatin remodeling and gene expression of pro-inflammatory mediators (3). It is proposed that ROS produced by phagocytes that have been recruited to the sites of inflammation are a major

cause of cell and tissue damage associated with many chronic inflammatory lung diseases including COPD (1).