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Chronic obstructive pulmonary disease is a heterogeneous disease caused by the interaction …


Biology Articles » Genetics » Clinical Genetics » The genetics of chronic obstructive pulmonary disease » Figures

Figures
- The genetics of chronic obstructive pulmonary disease

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Figure 1 The pathogenesis of COPD. Cigarette smoke activates macrophages (1), leading to the direct release of proteases or neutrophil chemotracctants (2), together with the release of oxidants resulting in subsequent breakdown of connective tissue in the lung (3), causing emphysema. Epithelial cell stimulation promotes fibroblast activity (4), eventually leading to small airways disease (5).

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Figure 2 Oxidative stress and its effects. Oxidants contained within cigarette smoke irritate epithelial cells (1), releasing activating cytokines that prompt the recruitment of neutrophils and the release of cell derived oxidants (2) and proteases (3). Antioxidants inhibit oxidant mediated damage to the lung (4), but when an imbalance arises (perhaps because of gene polymorphisms) oxidative stress results (5). The consequences of oxidative stress include activation of macrophages (6), leading to the production of more proteases, mucus hypersecretion, epithelial cell apoptosis, inflammation and inhibition of the action of antiproteases.

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Figure 3 Inflammatory mediators in COPD. There are many pro-inflammatory mediators involved in COPD, some of which are illustrated here. Cigarette smoke activates macrophages (1) to release TNFα, LTB4, IL8 and other neutrophil chemotactic factors (2), as well as proteases (3). TNFα promotes further IL8 release from other cells in the respiratory tract by NFκβ mediated effects on gene transcription (4). This increases local neutrophilic inflammation (5), and hence the release of proteases. Epithelial cells also stimulate fibroblasts via TGFβ, leading to fibrosis (6). TNF = tumour necrosis factor alpha, LTB4 = leukotriene B4, IL8 = interleukin 8, GRO = growth related oncogene, TGF = transforming growth factor, NF = nuclear factor

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