Cigarette smoke, the major environmental noxious agent, contains abundant amounts of oxygen-based free radicals, peroxides and peroxynitrite and results in severe oxidative stress in the lungs [6-9]. By oxidizing cellular proteins, lipids, DNA bases, enzymes and extracellular components such as matrix collagen and hyaluronic acid, these substances cause airway and parenchymal injury [10,11]. One of the consequences of the oxidative stress is chemotaxis, potent leucocyte adhesion and thus initiation of inflammation. The recruitment of inflammatory cells such as activated macrophages and neutrophils may also contribute to the oxidization by releasing specific enzymes [10-12].
Thus, cigarette smoke and the local release of oxidants initiate a vicious circle that may promote an 'abnormal' inflammatory response. For example, oxidants activate the transcription of nuclear factor-kB (NF-kB), which promotes genes of key inflammatory agents such as interleukin-8 (IL-8) and tumour necrosis factor-a (TNF-a) [13,14]. In addition, oxidants may oxidize antiproteases, resulting in a reduction of the antiprotease shield, and by activating matrix metalloproteinases may cause proteolysis [11,15]. Oxidative injury causes impairment to the barrier function of endothelial and epithelial cells [16,17]. Finally, if the oxidative stress is significant and prolonged, cells may undergo apoptosis or direct necrosis [18,19].
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