Apoptotic, inflammatory, and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung

D. van Berlo, V. Wilhelmi, A.W. Boots, M. Hullmann, T.A. Kuhlbusch, A. Bast, R.P. Schins, C. Albrecht

Research output: Contribution to journalArticleAcademicpeer-review

20 Citations (Scopus)

Abstract

There is increasing concern about the toxicity of inhaled multi-walled carbon nanotubes (MWCNTs). Pulmonary macrophages represent the primary cell type involved in the clearance of inhaled particulate materials, and induction of apoptosis in these cells has been considered to contribute to the development of lung fibrosis. We have investigated the apoptotic, inflammogenic, and fibrogenic potential of two types of MWCNTs, characterised by a contrasting average tube length and entanglement/agglomeration. Both nanotube types triggered H2O2 formation by RAW 264.7 macrophages, but in vitro toxicity was exclusively seen with the longer MWCNT. Both types of nanotubes caused granuloma in the mouse lungs. However, the long MWCNT induced a more pronounced pro-fibrotic (mRNA expression of matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1) and inflammatory (serum level of monocyte chemotactic protein-1) response. Masson trichrome staining also revealed epithelial cell hyperplasia for this type of MWCNT. Enhanced apoptosis was detected by cleaved caspase 3 immunohistochemistry in lungs of mice treated with the long and rigid MWCNT and, to a lesser extent, with the shorter, highly agglomerated MWCNT. However, staining was merely localised to granulomatous foci, and neither of the MWCNTs induced apoptosis in vitro, evaluated by caspase 3/7 activity in RAW 264.7 cells. In addition, our study reveals that the inflammatory and pro-fibrotic effects of MWCNTs in the mouse lung can vary considerably depending on their composition. The in vitro analysis of macrophage apoptosis appears to be a poor predictor of their pulmonary hazard.
Original languageEnglish
Pages (from-to)1725-1737
Number of pages13
JournalArchives of Toxicology
Volume88
Issue number9
DOIs
Publication statusPublished - Sep 2014

Keywords

  • Multi-walled carbon nanotubes
  • Lung
  • Macrophage
  • Apoptosis
  • Inflammation
  • Fibrosis
  • CROCIDOLITE ASBESTOS FIBERS
  • RAW 264.7 MACROPHAGES
  • IN-VITRO
  • INTRATRACHEAL INSTILLATION
  • GENE-EXPRESSION
  • NONFIBROUS PARTICLES
  • PLEURAL INFLAMMATION
  • MESOTHELIAL CELLS
  • HEME OXYGENASE-1
  • PULMONARY

Cite this

van Berlo, D. ; Wilhelmi, V. ; Boots, A.W. ; Hullmann, M. ; Kuhlbusch, T.A. ; Bast, A. ; Schins, R.P. ; Albrecht, C. / Apoptotic, inflammatory, and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung. In: Archives of Toxicology. 2014 ; Vol. 88, No. 9. pp. 1725-1737.
@article{fbef5fee9cba40f0ad1f9ad3e38adee9,
title = "Apoptotic, inflammatory, and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung",
abstract = "There is increasing concern about the toxicity of inhaled multi-walled carbon nanotubes (MWCNTs). Pulmonary macrophages represent the primary cell type involved in the clearance of inhaled particulate materials, and induction of apoptosis in these cells has been considered to contribute to the development of lung fibrosis. We have investigated the apoptotic, inflammogenic, and fibrogenic potential of two types of MWCNTs, characterised by a contrasting average tube length and entanglement/agglomeration. Both nanotube types triggered H2O2 formation by RAW 264.7 macrophages, but in vitro toxicity was exclusively seen with the longer MWCNT. Both types of nanotubes caused granuloma in the mouse lungs. However, the long MWCNT induced a more pronounced pro-fibrotic (mRNA expression of matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1) and inflammatory (serum level of monocyte chemotactic protein-1) response. Masson trichrome staining also revealed epithelial cell hyperplasia for this type of MWCNT. Enhanced apoptosis was detected by cleaved caspase 3 immunohistochemistry in lungs of mice treated with the long and rigid MWCNT and, to a lesser extent, with the shorter, highly agglomerated MWCNT. However, staining was merely localised to granulomatous foci, and neither of the MWCNTs induced apoptosis in vitro, evaluated by caspase 3/7 activity in RAW 264.7 cells. In addition, our study reveals that the inflammatory and pro-fibrotic effects of MWCNTs in the mouse lung can vary considerably depending on their composition. The in vitro analysis of macrophage apoptosis appears to be a poor predictor of their pulmonary hazard.",
keywords = "Multi-walled carbon nanotubes, Lung, Macrophage, Apoptosis, Inflammation, Fibrosis, CROCIDOLITE ASBESTOS FIBERS, RAW 264.7 MACROPHAGES, IN-VITRO, INTRATRACHEAL INSTILLATION, GENE-EXPRESSION, NONFIBROUS PARTICLES, PLEURAL INFLAMMATION, MESOTHELIAL CELLS, HEME OXYGENASE-1, PULMONARY",
author = "{van Berlo}, D. and V. Wilhelmi and A.W. Boots and M. Hullmann and T.A. Kuhlbusch and A. Bast and R.P. Schins and C. Albrecht",
year = "2014",
month = "9",
doi = "10.1007/s00204-014-1220-z",
language = "English",
volume = "88",
pages = "1725--1737",
journal = "Archives of Toxicology",
issn = "0340-5761",
publisher = "Springer",
number = "9",

}

Apoptotic, inflammatory, and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung. / van Berlo, D.; Wilhelmi, V.; Boots, A.W.; Hullmann, M.; Kuhlbusch, T.A.; Bast, A.; Schins, R.P.; Albrecht, C.

In: Archives of Toxicology, Vol. 88, No. 9, 09.2014, p. 1725-1737.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Apoptotic, inflammatory, and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung

AU - van Berlo, D.

AU - Wilhelmi, V.

AU - Boots, A.W.

AU - Hullmann, M.

AU - Kuhlbusch, T.A.

AU - Bast, A.

AU - Schins, R.P.

AU - Albrecht, C.

PY - 2014/9

Y1 - 2014/9

N2 - There is increasing concern about the toxicity of inhaled multi-walled carbon nanotubes (MWCNTs). Pulmonary macrophages represent the primary cell type involved in the clearance of inhaled particulate materials, and induction of apoptosis in these cells has been considered to contribute to the development of lung fibrosis. We have investigated the apoptotic, inflammogenic, and fibrogenic potential of two types of MWCNTs, characterised by a contrasting average tube length and entanglement/agglomeration. Both nanotube types triggered H2O2 formation by RAW 264.7 macrophages, but in vitro toxicity was exclusively seen with the longer MWCNT. Both types of nanotubes caused granuloma in the mouse lungs. However, the long MWCNT induced a more pronounced pro-fibrotic (mRNA expression of matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1) and inflammatory (serum level of monocyte chemotactic protein-1) response. Masson trichrome staining also revealed epithelial cell hyperplasia for this type of MWCNT. Enhanced apoptosis was detected by cleaved caspase 3 immunohistochemistry in lungs of mice treated with the long and rigid MWCNT and, to a lesser extent, with the shorter, highly agglomerated MWCNT. However, staining was merely localised to granulomatous foci, and neither of the MWCNTs induced apoptosis in vitro, evaluated by caspase 3/7 activity in RAW 264.7 cells. In addition, our study reveals that the inflammatory and pro-fibrotic effects of MWCNTs in the mouse lung can vary considerably depending on their composition. The in vitro analysis of macrophage apoptosis appears to be a poor predictor of their pulmonary hazard.

AB - There is increasing concern about the toxicity of inhaled multi-walled carbon nanotubes (MWCNTs). Pulmonary macrophages represent the primary cell type involved in the clearance of inhaled particulate materials, and induction of apoptosis in these cells has been considered to contribute to the development of lung fibrosis. We have investigated the apoptotic, inflammogenic, and fibrogenic potential of two types of MWCNTs, characterised by a contrasting average tube length and entanglement/agglomeration. Both nanotube types triggered H2O2 formation by RAW 264.7 macrophages, but in vitro toxicity was exclusively seen with the longer MWCNT. Both types of nanotubes caused granuloma in the mouse lungs. However, the long MWCNT induced a more pronounced pro-fibrotic (mRNA expression of matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1) and inflammatory (serum level of monocyte chemotactic protein-1) response. Masson trichrome staining also revealed epithelial cell hyperplasia for this type of MWCNT. Enhanced apoptosis was detected by cleaved caspase 3 immunohistochemistry in lungs of mice treated with the long and rigid MWCNT and, to a lesser extent, with the shorter, highly agglomerated MWCNT. However, staining was merely localised to granulomatous foci, and neither of the MWCNTs induced apoptosis in vitro, evaluated by caspase 3/7 activity in RAW 264.7 cells. In addition, our study reveals that the inflammatory and pro-fibrotic effects of MWCNTs in the mouse lung can vary considerably depending on their composition. The in vitro analysis of macrophage apoptosis appears to be a poor predictor of their pulmonary hazard.

KW - Multi-walled carbon nanotubes

KW - Lung

KW - Macrophage

KW - Apoptosis

KW - Inflammation

KW - Fibrosis

KW - CROCIDOLITE ASBESTOS FIBERS

KW - RAW 264.7 MACROPHAGES

KW - IN-VITRO

KW - INTRATRACHEAL INSTILLATION

KW - GENE-EXPRESSION

KW - NONFIBROUS PARTICLES

KW - PLEURAL INFLAMMATION

KW - MESOTHELIAL CELLS

KW - HEME OXYGENASE-1

KW - PULMONARY

U2 - 10.1007/s00204-014-1220-z

DO - 10.1007/s00204-014-1220-z

M3 - Article

VL - 88

SP - 1725

EP - 1737

JO - Archives of Toxicology

JF - Archives of Toxicology

SN - 0340-5761

IS - 9

ER -