title: Carbon black nanoparticles enhance bleomycin-induced lung inflammatory and fibrotic changes in mice.
abstract: With the recent increasing use of nanoparticles, there is concern that they may become an environmental risk factor as airborne particles. However, the impact of these particles on susceptible subjects with predisposing lung disease have not been sufficiently elucidated. In the present study, we investigated the effects of nanoparticles on pulmonary inflammatory and fibrotic changes induced by intratracheal bleomycin (BLM) challenge in mice. Mice were intratracheally administered either vehicle, 14-nm carbon black nanoparticles (CBNPs), BLM or BLM plus CBNP. First, we assessed lung collagen content, lung compliance and fibrotic changes in histopathology on day 21 after instillation. Then, to elucidate how CBNP contributes to the development of BLM-induced fibrosis, we collected bronchoalveolar lavage (BAL) fluid on days 2, 7, 14 and 21 and determined the total and differential cell counts and concentrations of two proinflammatory cytokines (keratinocyte chemoattractant [KC] and interleukin [IL]-6) and two fibrogenic mediators (CC chemokine ligand 2 [CCL2] and transforming growth factor-β(1) [TGF-β(1)]). Expression of nitrotyrosine, an indicator of oxidant injury, was also evaluated on days 7 and 21. CBNP, when combined with BLM, significantly enhanced BLM-induced increase in lung collagen content, decrease in lung compliance, and fibrotic changes in histopathology. CBNP significantly augmented BLM-induced increase in the numbers of inflammatory cells in BAL fluid on days 2 and 7 and levels of KC and IL-6 on day 2. In addition, CBNP administered in combination with BLM significantly elevated the levels of CCL2 on days 2, 7 and 14, and TGF-β(1) on day 14 in BAL fluid as compared with BLM alone. Nitrotyrosine expression was also increased by BLM plus CBNP compared with BLM alone. In contrast, CBNP did not exert any significant effect on these parameters by itself. These results indicate that CBNP can exaggerate BLM-induced inflammatory and fibrotic changes in the lung, suggesting the potential impact of nanoparticles on lung inflammation and fibrosis.
authors.affiliation: Division of Pulmonary Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kamata
authors.forename: Sadatomo
authors.initials: S
authors.lastname: Tasaka
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakano
authors.forename: Hiromi
authors.initials: H
authors.lastname: Shinoda
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kimizuka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishii
authors.forename: Naoki
authors.initials: N
authors.lastname: Hasegawa
authors.forename: Rina
authors.initials: R
authors.lastname: Takamiya
authors.forename: Seitaro
authors.initials: S
authors.lastname: Fujishima
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D006651:Histocytochemistry; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D053758:Nanoparticles / Q000008:administration & dosage; D053260:Soot / Q000633:toxicity*
chemical_list: D016207:Cytokines; D053260:Soot; D001761:Bleomycin