Dispersal state of multiwalled carbon nanotubes elicits profibrogenic cellular responses that correlate with fibrogenesis biomarkers and fibrosis in the murine lung

Authors

Xiang Wang, University of California, Los Angeles
Tian Xia, University of California, Los Angeles
Susana Addo Ntim, New Jersey Institute of Technology
Zhaoxia Ji, University of California, Los Angeles
Sijie Lin, University of California, Los Angeles
Huan Meng, University of California, Los Angeles
Choong Heui Chung, University of California, Los Angeles
Saji George, University of California, Los Angeles
Haiyuan Zhang, University of California, Los Angeles
Meiying Wang, University of California, Los Angeles
Ning Li, University of California, Los Angeles
Yang Yang, University of California, Los Angeles
Vincent Castranova, National Institute for Occupational Safety and Health
Somenath Mitra, New Jersey Institute of Technology
James C. Bonner, NC State University
André E. Nel, University of California, Los Angeles

Document Type

Article

Publication Date

12-27-2011

Abstract

We developed a dispersal method for multiwalled carbon nanotubes (MWCNTs) that allows quantitative assessment of dispersion on profibrogenic responses in tissue culture cells and in mouse lung. We demonstrate that the dispersal of as-prepared (AP), purified (PD), and carboxylated (COOH) MWCNTs by bovine serum albumin (BSA) and dipalmitoylphosphatidylcholine (DPPC) influences TGF-β1, PDGF-AA, and IL-1β production in vitro and in vivo. These biomarkers were chosen based on their synergy in promoting fibrogenesis and cellular communication in the epithelial-mesenchymal cell trophic unit in the lung. The effect of dispersal was most noticeable in AP- and PD-MWCNTs, which are more hydrophobic and unstable in aqueous buffers than hydrophilic COOH-MWCNTs. Well-dispersed AP- and PD-MWCNTs were readily taken up by BEAS-2B, THP-1 cells, and alveolar macrophages (AM) and induced more prominent TGF-β1 and IL-1β production in vitro and TGF-β1, IL-1β, and PDGF-AA production in vivo than nondispersed tubes. Moreover, there was good agreement between the profibrogenic responses in vitro and in vivo as well as the ability of dispersed tubes to generate granulomatous inflammation and fibrosis in airways. Tube dispersal also elicited more robust IL-1β production in THP-1 cells. While COOH-MWCNTs were poorly taken up in BEAS-2B and induced little TGF-β1 production, they were bioprocessed by AM and induced less prominent collagen deposition at sites of nongranulomatous inflammation in the alveolar region. Taken together, these results indicate that the dispersal state of MWCNTs affects profibrogenic cellular responses that correlate with the extent of pulmonary fibrosis and are of potential use to predict pulmonary toxicity. © 2011 American Chemical Society.

Identifier

84555163703 (Scopus)

Publication Title

ACS Nano

External Full Text Location

https://doi.org/10.1021/nn2033055

e-ISSN

1936086X

ISSN

19360851

PubMed ID

22047207

First Page

9772

Last Page

9787

Issue

12

Volume

5

Grant

R01ES016746

Fund Ref

National Institute of Environmental Health Sciences

Recommended Citation

Wang, Xiang; Xia, Tian; Addo Ntim, Susana; Ji, Zhaoxia; Lin, Sijie; Meng, Huan; Chung, Choong Heui; George, Saji; Zhang, Haiyuan; Wang, Meiying; Li, Ning; Yang, Yang; Castranova, Vincent; Mitra, Somenath; Bonner, James C.; and Nel, André E., "Dispersal state of multiwalled carbon nanotubes elicits profibrogenic cellular responses that correlate with fibrogenesis biomarkers and fibrosis in the murine lung" (2011). Faculty Publications. 10947.
https://digitalcommons.njit.edu/fac_pubs/10947