title: Endocytosis of Multiwalled Carbon Nanotubes in Bronchial Epithelial and Mesothelial Cells.
abstract: Bronchial epithelial cells and mesothelial cells are crucial targets for the safety assessment of inhalation of carbon nanotubes (CNTs), which resemble asbestos particles in shape. Intrinsic properties of multiwalled CNTs (MWCNTs) are known to cause potentially hazardous effects on intracellular and extracellular pathways. These interactions alter cellular signaling and affect major cell functions, resulting in cell death, lysosome injury, reactive oxygen species production, apoptosis, and cytokine release. Furthermore, CNTs are emerging as a novel class of autophagy inducers. Thus, in this study, we focused on the mechanisms of MWCNT uptake into the human bronchial epithelial cells (HBECs) and human mesothelial cells (HMCs). We verified that MWCNTs are actively internalized into HBECs and HMCs and were accumulated in the lysosomes of the cells after 24-hour treatment. Next, we determined which endocytosis pathways (clathrin-mediated, caveolae-mediated, and macropinocytosis) were associated with MWCNT internalization by using corresponding endocytosis inhibitors, in two nonphagocytic cell lines derived from bronchial epithelial cells and mesothelioma cells. Clathrin-mediated endocytosis inhibitors significantly suppressed MWCNT uptake, whereas caveolae-mediated endocytosis and macropinocytosis were also found to be involved in MWCNT uptake. Thus, MWCNTs were positively taken up by nonphagocytic cells, and their cytotoxicity was closely related to these three endocytosis pathways.
authors.affiliation: Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Maruyama
authors.affiliation: Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan ; Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Hisao
authors.identifier: 0000-0001-5195-9711
authors.initials: H
authors.lastname: Haniu
authors.affiliation: Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Naoto
authors.identifier: 0000-0001-6424-087X
authors.initials: N
authors.lastname: Saito
authors.affiliation: Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Saitama 362-0806, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Department of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Tamotsu
authors.identifier: 0000-0002-8754-2202
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Aoki
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Takanashi
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001194:Asbestos / Q000633:toxicity; D001343:Autophagy / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D004705:Endocytosis / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D008654:Mesothelioma / Q000139:chemically induced / Q000473:pathology*; D037742:Nanotubes, Carbon / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D001194:Asbestos