Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study.
Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To determine potential signaling pathways involved with MWCNT-associated pathological changes in comparison to asbestos, up- and down-regulated gene expression was determined in lung tissue at 1 yr postexposure. Exposure to MWCNT tended to favor those pathways involved in immune responses, specifically T-cell responses, whereas exposure to asbestos tended to favor pathways involved in oxygen species production, electron transport, and cancer. Data indicate that MWCNT are biopersistent in the lung and induce inflammatory and fibrotic pathological alterations similar to those of crocidolite asbestos, but may reach these endpoints by different mechanisms.
a Pathology and Physiology Research Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , West Virginia , USA.
Brandi N
BN
Snyder-Talkington
b Mary Babb Randolph Cancer Center , West Virginia University , Morgantown , West Virginia , USA.
Chunlin
C
Dong
a Pathology and Physiology Research Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , West Virginia , USA.
Dale W
DW
Porter
c Department of Pathology , West Virginia University , Morgantown , West Virginia , USA.
Barbara
B
Ducatman
a Pathology and Physiology Research Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , West Virginia , USA.
Michael G
MG
Wolfarth
a Pathology and Physiology Research Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , West Virginia , USA.
Michael
M
Andrew
a Pathology and Physiology Research Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , West Virginia , USA.
Lori
L
Battelli
b Mary Babb Randolph Cancer Center , West Virginia University , Morgantown , West Virginia , USA.
Rebecca
R
Raese
d Department of Pharmaceutical Sciences , School of Pharmacy, West Virginia University , Morgantown , West Virginia , USA.
Vincent
V
Castranova
b Mary Babb Randolph Cancer Center , West Virginia University , Morgantown , West Virginia , USA.
Nancy L
NL
Guo
a Pathology and Physiology Research Branch, Health Effects Laboratory Division , National Institute for Occupational Safety and Health , Morgantown , West Virginia , USA.
Yong
Y
Qian
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D019570:Inhalation Exposure; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon / Q000633:toxicity*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D013997:Time Factors
D000393:Air Pollutants; D037742:Nanotubes, Carbon; D017638:Asbestos, Crocidolite; D007770:L-Lactate Dehydrogenase