title: Effects of inhaled nanoparticles on acute lung injury induced by lipopolysaccharide in mice.
abstract: We have previously shown that intratracheal instillation of carbon nanoparticles exacerbates lung inflammation related to bacterial endotoxin (lipopolysaccharide, LPS) and subsequent systemic inflammation with coagulatory disturbance in mice [Inoue, K., Takano, H., Yanagisawa, R., Hirano, S., Sakurai, M., Shimada, A., Yoshikawa, T., 2006b. Effects of airway exposure to nanoparticles on lung inflammation induced by bacterial endotoxin in mice. Environ. Health Perspect. 114, 1325-1330]. The present study was performed to determine whether inhalation of diesel engine-derived nanoparticles also exacerbates the model. ICR mice were exposed for 5h to clean air or diesel engine-derived nanoparticles at a concentration of 15, 36, or 169 microg/m(3) after intratracheal challenge with 125 microg/kg of LPS or vehicle, and were sacrificed for evaluation 24h after the intratracheal challenge. Nanoparticles alone did not induce lung inflammation. Nanoparticle inhalation increased LPS-elicited inflammatory cell recruitment into the bronchoalveolar lavage fluid and lung parenchyma as compared with clean air inhalation in a concentration-dependent manner. Lung homogenates derived from the nanoparticle+LPS groups tended to have increased tumor necrosis factor-alpha level and chemotaxis activity for polymorphonuclear leukocytes as compared to those from the LPS group or the corresponding nanoparticle groups. Nanoparticle inhalation did not significantly increase lung expression of proinflammatory cytokines or facilitate systemic inflammation and coagulatory disturbance. Isolated alveolar macrophages (AMs) from nanoparticle-exposed mice showed greater production of interleukin-1beta and keratinocyte chemoattractant stimulated with ex vivo LPS challenge than those from clean air-exposed mice, although the differences did not reach statistical significance. These results suggest that acute exposure to diesel nanoparticles exacerbates lung inflammation induced by LPS.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan. inoue.kenichirou@nies.go.jp
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Seishiro
authors.initials: S
authors.lastname: Hirano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimada
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000208:Acute Disease; D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018932:Chemokine CCL2 / Q000032:analysis; D054407:Chemokine CCL4; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D053583:Interleukin-1beta / Q000032:analysis; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology*; D011486:Protein C / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D001335:Vehicle Emissions; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D011486:Protein C; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; D014841:von Willebrand Factor