Takamitsu Miyayama    Department   School of Medicine, School of Medicine    Position   Assistant Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Difference in the toxicity mechanism between ion and nanoparticle forms of silver in the mouse lung and in macrophages
Journal	Formal name：Toxicology Abbreviation：Toxicology
Volume, Issue, Page	328,pp.84-92
Author and coauthor	ARAI Yuta†, MIYAYAMA Takamitsu, HIRANO Seishiro*
Authorship	2nd author
Publication date	2015/02
Summary	The health effects of silver nanoparticles (AgNPs) have not been well investigated, despite AgNPs being now widely used in consumer products. We investigated the metabolic behavior and toxicity of AgNPs in comparison to silver nitrate (AgNO3) both in vivo and in vitro. AgNPs (20 nm diameter) in 1% albumin solution or AgNO3 solution were injected into mouse lungs. AgNPs appeared not to be absorbed by the lung tissue, whereas 7% of the initial dose was recovered in the liver of the AgNO3-exposed mice 4 h after administration, suggesting that the ionic form of silver was absorbed by the lung tissue and entered the systemic circulation. The pro-inflammatory cytokine, IL-1β, and neutrophils in bronchoalveolar lavage fluid (BALF) increased following intratracheal instillation of AgNPs or AgNO3. AgNO3 recruited more neutrophils in the alveolar space than did AgNPs. In an in vitro study, AgNO3 was more cytotoxic than 20, 60, or 100 nm diameter AgNPs in a mouse macrophage cell line (J774.1). To investigate the intracellular distribution of Ag in detail, the distribution of Ag to cytosolic proteins was studied using HPLC-ICPMS in J774.1 cells following exposure to AgNO3 or 20 nm AgNPs. Ag was mainly distributed to metallothioneins (MT) and to high molecular weight proteins in AgNO3- and AgNPs-exposed cells, respectively. Confocal laser micro-scopic examination of LysoTracker-labeled cells indicated that AgNPs were colocalized with lysosomes in J774.1 cells. These results suggest that AgNPs were transported to lysosomes and only gradually dissolved in the macrophages, causing milder inflammatory stimulation of the lung compared to AgNO3.
DOI	doi: 10.1016/j.tox.2014.12.014