Pulmonary Exposure to Diesel Exhaust Particles Enhances Coagulatory Disturbance with Endothelial Damage and Systemic Inflammation Related to Lung Inflammation

Abstract

Pulmonary exposure to diesel exhaust particles (DEP) enhances lung inflammation related to bacterial endotoxin (lipopolysaccharide [LPS]) in mice. Severe lung inflammation can reportedly induce coagulatory abnormalities and systemic inflammation. This study examined the effects of components of DEP on lung inflammation, pulmonary permeability, coagulatory changes, systemic inflammatory response, and lung-to-systemic translocation of LPS in a murine model of lung inflammation. ICR mice were divided into six experimental groups that intratracheally received vehicle, LPS (2.5 mg/kg), organic chemicals in DEP (DEP-OC; 4 mg/kg) extracted with dicloromethane), residual carbonaceous nuclei of DEP (washed DEP: 4 mg/kg), DEP-OC + LPS, or washed DEP + LPS. Both DEP components exacerbated lung inflammation, vascular permeability, and the increased fibrinogen and E-selectin levels induced by LPS. With overall trends, the exacerbation was more prominent with washed DEP than with DEP-OC. Washed DEP + LPS significantly decreased activated protein C and antithrombin-III and elevated circulatory levels of interleukin (IL)-6, keratinocyte chemoattractant (KC), and LPS as compared with LPS alone, whereas DEP-OC + LPS elevated IL-6, KC, and LPS without significance. These results show that DEP components, especially washed DEP, amplify the effects if LPS on the respiratory system and suggest that they contribute to the adverse health effects of particulate air pollution on the sensitive populations with predisposing vascular and/or pulmonary diseases, including ischemic vascular diseases and respiratory infection.

Promoting effects of nanoparticles/materials on sensitive lung inflammatory diseases

“…In addition, one intriguing aspect of the epidemiologic data is that health effects of PM 2.5 are primarily seen in subjects with predisposing factors, including pneumonia, asthma, chronic obstructive pulmonary disease, compromised immune systems, and age over 65 years old [3]. Consistent with the epidemiological studies, we have experimentally demonstrated that diesel exhaust particles (DEP), major contributors to environmental PM 2.5 in urban areas, exhibit respiratory toxicity with or without predisposing factors in vivo [4][5][6][7][8][9][10].…”

“…In addition, LPS is a significant constituent of many air pollutant particles and has accordingly been implicated in the adverse effects of PM [33]. In accordance with the close links among LPS, lung inflammation (injury), and PM, we have previously shown that intratracheal administration of DEP and their components facilitates lung inflammation induced by LPS [8,34] and subsequent systemic inflammation with coagulatory disturbance [9].…”

Effects of diesel exhaust particles on coagulation

“…In our study, we observed that a single pulmonary exposure to DEP (8 mg·kg À1 ) significantly increased the serum level of fibrinogen (4.261 ± 0.248 g·L À1 ; unpublished data), which is involved in fibrin (clot) formation, as compared to that of vehicle (3.356 ± 0.110 g·L À1 ). Interestingly, the carbonaceous nuclei of DEP obtained after extraction with dichloromethane (CH 2 Cl 2 : referred to as 'washed DEP' 4 mg·kg À1 ) further increased the level of fibrinogen (4.883 ± 0.371 g·L À1 ) in the same experiment (Inoue et al, 2006), suggesting that the organic chemical component in DEP extracted with CH 2 Cl 2 (referred to as 'DEP-OC') includes elements that have the potential to suppress the synthesis of fibrinogen. Therefore, it should be noted that the role each individual DEP component plays in the regulation of the coagulation system and resultant vascular thrombotic events induced by DEP is complicated.…”

Cytokine response to diabetic ketoacidosis (DKA) in children with type 1 diabetes (T1DM)

“…Thus it has been shown that IL-6 triggers production of metalloproteinase inhibitors, such as alpha 2-macroglobulin by perivascular astrocytes [17], resulting in BBB failure and perivascular cerebral edema. Also elevated circulating levels of IL-6 have been reported to enhance pulmonary permeability and endothelial damage in different conditions, such as ischemia-perfusion during lung transplantation [18], pulmonary exposure to diesel [19], or intestinal ischemia [20]. Moreover other proinflammatory cytokines, such as TNF-α, IL-1β and IFN-γ (Interferon-γ) have been shown to increase pulmonary permeability, resulting in pulmonary edema [21].…”