Biochemical and physiological effects from exhaust emissions Biochemical and physiological effects from exhaust emissions. A review of the relevant literature  Sergio Manzetti, Otto Andersen  Pathophysiology  Volume 23, Issue 4, Pages 285-293 (December 2016) DOI: 10.1016/j.pathophys.2016.10.002 Copyright © 2016 Elsevier B.V. Terms and Conditions

Fig. 1 The Cadherin-Adiponectin mechanisms during PM10 intoxication. The chart shows how lung cells release cadherin 13 proteins from the cell surface during PM10 intoxication and how this is directly linked with adiponectin function. Once cadherin 13 is transferred into the blood during PM10 intoxication, it can affect adiponectin function by possibly interfering with insulin transport. Pathophysiology 2016 23, 285-293DOI: (10.1016/j.pathophys.2016.10.002) Copyright © 2016 Elsevier B.V. Terms and Conditions

Fig. 2 Part of the immunological mechanism used by a lung cell in response to exhaust emissions. The figure shows the major responses associated with air pollution intoxication. The DNA expresses cytokines as a response to ultrafine particles, PM2.5 and PM10, from air pollution. Concomitantly, the cell expresses reactive oxygen species (ROX) to hydrolyse NO2 to NO in a reaction with water. The production of NO outside the cell precipitates further reactions, which are not shown here for graphical simplicity. The expression of TNF-α is a central response to oxidative stress, which prevents tumor growth. A third stressor for the cell is reduction of cellular oxygen, to which it responds by expressing lactate dehydrogenase and other factors, which maintain pH balance in the cell. Pathophysiology 2016 23, 285-293DOI: (10.1016/j.pathophys.2016.10.002) Copyright © 2016 Elsevier B.V. Terms and Conditions

Fig. 3 Possible mechanism of DNA damage by ultrafine carbon nanoparticles. To protect the DNA during oxidative stress, the DNA methylation enzymes DNAMT3A and 3B are expressed [53]. When this mechanism fails due to excess stress from carbon black nanoparticles (BC), the gene for glutathione synthetase is not protected and mutations can occur. This can reduce the levels of glutathione produced by the cell to defend itself from oxidative stress. The cell’s natural defense against ultrafine nanoparticles, the production of ROX by oxidoreductases, also increases the levels of ROX inside the cell, which further disturbs the DNA-protecting mechanism brought into play by DNAMT3A and DNAMT3B expression, as shown above. Pathophysiology 2016 23, 285-293DOI: (10.1016/j.pathophys.2016.10.002) Copyright © 2016 Elsevier B.V. Terms and Conditions

Fig. 4 A possible mechanism leading to lung cancer triggered by air pollution exposure. Healthy lung cells express normal levels of DNA regulating factors. The ROS-exposed cell induces the expression of beta-integrins after cross-talk between ROS species and nuclear factor-kappa B proteins. The expression and activation of integrins cross-interacts with DNA-regulating pathways (not shown for graphical simplicity) leading to the formation of migrating lung cancer cells, which promotes extracellular matrix (ECM) degrading proteins, connective tissue growth factor (CTFG), transforming growth factor beta (TGF-beta), and interleukins. Pathophysiology 2016 23, 285-293DOI: (10.1016/j.pathophys.2016.10.002) Copyright © 2016 Elsevier B.V. Terms and Conditions

Fig. 5 The relationship between inflammation and various stages of disease progression upon prolonged exposure to exhaust emissions. Histamines, GPCR, Protein Kinase C, and G-protein are four central components of the vasoconstriction mechanism inherent to airway tissues [124–127]. The main classes of principal proteins that protect the DNA, modify the DNA, and prevent and/or trigger cell growth can be simplified to the Cytochrome P450 system, the hypoxia-inducible genes, the tumor-necrosis factor family, and the family of integrins [39,44,78,128]. Pathophysiology 2016 23, 285-293DOI: (10.1016/j.pathophys.2016.10.002) Copyright © 2016 Elsevier B.V. Terms and Conditions