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Fig. 2 | Journal of Nanobiotechnology

Fig. 2

From: Novel drug delivery systems targeting oxidative stress in chronic obstructive pulmonary disease: a review

Fig. 2

Cigarette smoke-related vascular irritation and activation in patients with COPD. Oxidative irritants including tobacco smoke have a direct effect on the epithelial cells, macrophages, and oedematous basal membranes. The airway smooth muscle markedly increased under excess exposure to ROS. Irritants activate macrophages to release several chemotactic factors including CCL2, which attract inflammatory cells to the lungs and acts on CCR2 to attract monocytes. LTB, CXCL1, and CXCL8 act on CCR2 to attract neutrophils. Neutrophil elastase causes hypersecretion of mucus. CXCL9, CXCL10, and CXCL11 act on CXCR 3, which attracts TH1 and TC 1 cells. TC1 cells, through the release of perforin and granzyme B, induce apoptosis of type I pneumocytes, thereby contributing to emphysema. IFNγ and TNFα released by TH1 stimulate inflammation. Activated macrophages provide oxidative signalling to neutrophils and TH1 cells, which cause an imbalance in the protease/antiprotease system and overexpression of MMP-9 and Ne. The increased expression of Ne induces TNF-α by the NF-κB signalling pathway and accelerates apoptosis of epithelial cells. Oxidative stress activates P13K leading to the phosphorylation and inactivation of HDAC2. Macrophages generate ROS and NO that form ONOO-peroxynitrite and might also inhibit the activity of HDAC2. These modifications of HDAC2 result in corticosteroid resistance in COPD patients. Oxidative stress also drives accelerated ageing through the activation of P13K and reduction in sirtuin-1 levels, which leads to cellular senescence and release of inflammatory proteins, further increasing oxidative stress. ROS can induce tachykinin release from the capsaicin-sensitive sensory that acts on the neurokinin receptors in the airways to induce bronchial hyperresponsiveness. P13K, phosphoinositide 3-kinase; IL, interleukin; TGF, transforming growth factor; MMP, matrix metalloproteinase; MUC5AC; Ne, neutrophil elastase; ROS, reactive oxygen species; CCL, CC-chemokine ligand; CCR, CC-chemokine receptor; CXCL, CXC-chemokine ligand; CXCR, CXC-chemokine receptor; TH1, T helper1 cells; TC1, type 1 cytotoxic; NO, nitric oxide; ONOO, peroxynitrite

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