title: Pulmonary persistence of graphene nanoplatelets may disturb physiological and immunological homeostasis.
abstract: Accumulated evidence suggests that chronic pulmonary accumulation of harmful particles cause adverse pulmonary and systemic health effects. In our previous study, most of the graphene nanoplatelet (GNP) remained in the lung until 28 days after a single instillation. In this study, we sought to evaluate the local and systemic health effect after a long pulmonary persistence of GNP. As expected, GNP remained in the lung on day 90 after a single intratracheal instillation (1.25, 2.5 and 5 mg kg-1). In the lung exposed at the highest dose, the total number of cells and the percentage of lymphocytes significantly increased in the BAL fluid with an increase in both the number of GNP-engulfed macrophages and the percentage of apoptotic cells. A Th1-shifted immune response, the elevated chemokine secretion and the enhanced expression of cytoskeletal-related genes were observed. Additionally, the expression of natriuretic-related genes was noteworthy altered in the lungs. Moreover, the number of white blood cells (WBC) and the percentage of macrophages and neutrophils clearly increased in the blood of mice exposed to a 5-mg kg-1dose, whereas total protein, BUN and potassium levels significantly decreased. In conclusion, we suggest that the long persistence of GNP in the lung may cause adverse health effects by disturbing immunological- and physiological-homeostasis of our body. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Myunggok Eye Research Institute, Konyang University, Daejeon, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Inhalation Toxicology Center, Korea Institute of Toxicology, Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Inhalation Toxicology Center, Korea Institute of Toxicology, Korea.
authors.forename: Kyuhong
authors.initials: K
authors.lastname: Lee
authors.affiliation: Nano-Electron Creative Research Center, Electronics and Telecommunications Research Institute, Daejeon, Korea.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Choi
authors.affiliation: Toxicologic Pathology Center, Korea Institute of Toxicology, Daejeon, Korea.
authors.forename: Byoung-Seok
authors.initials: BS
authors.lastname: Lee
authors.affiliation: School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul, Korea.
authors.forename: Gwang-Hee
authors.initials: GH
authors.lastname: Lee
authors.affiliation: School of Civil, Environmental, and Architectural Engineering, Korea University, Seoul, Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006108:Graphite / Q000378:metabolism / Q000633:toxicity*; D006706:Homeostasis / Q000187:drug effects* / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D049329:Nanostructures / Q000633:toxicity*; D058408:Th1-Th2 Balance / Q000187:drug effects*
chemical_list: D006108:Graphite
keywords: Graphene; antigen presentation; immune regulation; immunotoxicity; nanoplatelets; physiology