title: 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.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Miho
authors.initials: M
authors.lastname: Sakurai
authors.forename: Toshio
authors.initials: T
authors.lastname: Oda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamura
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimada
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D002545:Brain Ischemia / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D002630:Chemotactic Factors / Q000378:metabolism; D019040:E-Selectin / Q000097:blood; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D005340:Fibrinogen / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D010316:Particle Size; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology; D011486:Protein C / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000473:pathology*; D012141:Respiratory Tract Infections / Q000473:pathology; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D002630:Chemotactic Factors; D019040:E-Selectin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011486:Protein C; D001335:Vehicle Emissions; D000990:Antithrombin III; D005340:Fibrinogen