Pro-Inflammatory and Pro-Fibrogenic Effects of Ionic and Particulate Arsenide and Indium-Containing Semiconductor Materials in the Murine Lung.
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 it 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 submicron 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 the murine lung 40 h and 21 days 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 1β (IL-1β) by nanosized (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 days 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 subacute effects. Importantly, the difference between the 40 h and 21 days 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)3nanostructures. 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 InCl3species 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.
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
Wen
0000-0003-2083-2069
W
Jiang
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
Xiang
X
Wang
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
Olivia J
OJ
Osborne
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
Yingjie
Y
Du
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
Chong Hyun
CH
Chang
Division of NanoMedicine, Department of Medicine, University of California Los Angeles , 10833 Le Conte Ave, Los Angeles, California 90095, United States.
Yu-Pei
YP
Liao
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
Bingbing
0000-0002-5444-5078
B
Sun
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
Jinhong
J
Jiang
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.
Zhaoxia
Z
Ji
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.|School of Radiation Medicine and Protection and School for Radiological and Interdisciplinary Sciences (RAD-X), Medical College of Soochow University , Suzhou, Jiangsu 215123, China.
Ruibin
0000-0001-6471-7658
R
Li
Division of NanoMedicine, Department of Medicine, University of California Los Angeles , 10833 Le Conte Ave, Los Angeles, California 90095, United States.
Xiangsheng
X
Liu
Division of NanoMedicine, Department of Medicine, University of California Los Angeles , 10833 Le Conte Ave, Los Angeles, California 90095, United States.
Jianqin
J
Lu
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.|College of Environmental Science and Engineering State Key Laboratory of Pollution Control and Resource Reuse, Tongji University , Shanghai 200092, China.
Sijie
0000-0002-6970-8221
S
Lin
Division of NanoMedicine, Department of Medicine, University of California Los Angeles , 10833 Le Conte Ave, Los Angeles, California 90095, United States.
Huan
H
Meng
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.|Division of NanoMedicine, Department of Medicine, University of California Los Angeles , 10833 Le Conte Ave, Los Angeles, California 90095, United States.
Tian
T
Xia
Center for Environmental Implications of Nanotechnology, California NanoSystems Institute, University of California Los Angeles , 570 Westwood Plaza, Los Angeles, California 90095, United States.|Division of NanoMedicine, Department of Medicine, University of California Los Angeles , 10833 Le Conte Ave, Los Angeles, California 90095, United States.
André E
AE
Nel
D000818:Animals; D001152:Arsenicals / Q000737:chemistry*; D002460:Cell Line; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007204:Indium / Q000737:chemistry* / Q000633:toxicity; D007249:Inflammation / Q000378:metabolism*; D007477:Ions / Q000737:chemistry / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D012666:Semiconductors; D013499:Surface Properties; D000074084:THP-1 Cells
D001152:Arsenicals; D007477:Ions; D007204:Indium; D005340:Fibrinogen
III−V materials; lung fibrosis; lung inflammation; occupational disease; pro-inflammatory cytokine; size