Pro-Inflammatory and Pro-Fibrogenic Effects of Ionic and Particulate Arsenide and Indium-Containing Semiconductor Materials in the Murine Lung

  • Authors:
    Wen Jiang (UCLA), Olivia Osborne (UCLA), Andre Nel (UCLA), Xiang Wang (UCLA), Yingjie Du (UCLA), Chong Hyun Chang (UCLA), Yu-Pei Liao (UCLA), Bingbing Sun (UCLA), Jinhing Jiang (UCLA), Zhaoxia Ji (UCLA), Ruibin Li (UCLA), Xiangsheng Liu (UCLA), Jianqin Lu (UCLA), Sijie Lin (UCLA), Huan Meng (UCLA), Tian Xia (UCLA)
    Publication ID:
    P090711
    Publication Type:
    Paper
    Received Date:
    17-Apr-2017
    Last Edit Date:
    17-Apr-2017
    Research:
    425.050 (University of California/Los Angeles)

Abstract

We have recently shown that the toxicological potential of GaAs and InAs particulates in cells is size- and dissolution-dependent, tending to be more pronounced for nano- vs. micron-sized particles. Whether the size-dependent dissolution and shedding of ionic III-V materials also apply to pulmonary exposure is unclear. While has been demonstrated that micron-sized III-V particles, such as GaAs and InAs, are capable of inducing hazardous pulmonary effects in an occupational setting, as well as in animal studies, the effect of sub-micron particles (e.g., the removal of asperities during processing of semiconductor wafers) is unclear. We used cytokine profiling to compare the pro-inflammatory effects of micron- and nanoscale GaAs and InAs particulates in cells as well as murine lung 40 h and 21 days (D) after oropharyngeal aspiration. Use of cytokine array technology in macrophage and epithelial cell cultures demonstrated a proportionally higher increase in the levels of matrix metalloproteinase inducer (EMMPRIN), macrophage migration inhibitory factor (MIF), and Interleukin IL-1β by nano-sized (n) GaAs and n-InAs as well as As(III). n-GaAs and n-InAs also triggered higher neutrophil counts in the bronchoalveolar lavage fluid (BALF) of mice than micronscale particles 40 h post-aspiration, along with increased production of EMMPRIN and MIF. In contrast, in animals sacrificed 21 D after exposure, only n-InAs induced fibrotic lung changes as determined by increased lung collagen as well as increased levels of TGF-β1 and PDGF-AA in the BALF. A similar trend was seen for EMMPRIN and matrix metallopeptidase (MMP-9) levels in the BALF. Nano- and micron-GaAs had negligible sub-acute effects. Importantly, the difference between the 40 h and 21 D data appears to be biopersistence of n-InAs, as demonstrated by ICP-OES analysis of lung tissue. Interestingly, an ionic form of In, InCl3, also showed pro-fibrogenic effects due to the formation of insoluble In(OH)3 nanostructures. All considered, these data indicate that while nanoscale particles exhibit increased pro-inflammatory effects in the lung, most effects are transient, except for n-InAs and insoluble InCl3 species that are biopersistent and trigger pro-fibrotic effects. These results are of potential importance for the understanding the occupational health effects of III-V particulates.

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