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Extrapulmonary transport of MWCNT following inhalation exposure.

Mercer RR, Scabilloni JF, Hubbs AF, Wang L, Battelli LA, McKinney W, Castranova V, Porter DW - Part Fibre Toxicol (2013)

Bottom Line: Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively.The burden of singlet MWCNT in the lymph nodes, diaphragm, chest wall and extrapulmonary organs at 336 days post-exposure was significantly higher than at 1 day post-exposure.The tracheobronchial lymph nodes contain high levels of MWCNT following exposure and further accumulate over nearly a year to levels that are a significant fraction of the lung burden 1 day post-exposure.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Inhalation exposure studies of mice were conducted to determine if multi-walled carbon nanotubes (MWCNT) distribute to the tracheobronchial lymphatics, parietal pleura, respiratory musculature and/or extrapulmonary organs. Male C57BL/6 J mice were exposed in a whole-body inhalation system to a 5 mg/m3 MWCNT aerosol for 5 hours/day for 12 days (4 times/week for 3 weeks, lung burden 28.1 ug/lung). At 1 day and 336 days after the 12 day exposure period, mice were anesthetized and lungs, lymph nodes and extrapulmonary tissues were preserved by whole body vascular perfusion of paraformaldehyde while the lungs were inflated with air. Separate, clean-air control groups were studied at 1 day and 336 days post-exposure. Sirius Red stained sections from lung, tracheobronchial lymph nodes, diaphragm, chest wall, heart, brain, kidney and liver were analyzed. Enhanced darkfield microscopy and morphometric methods were used to detect and count MWCNT in tissue sections. Counts in tissue sections were expressed as number of MWCNT per g of tissue and as a percentage of total lung burden (Mean ± S.E., N = 8 mice per group). MWCNT burden in tracheobronchial lymph nodes was determined separately based on the volume density in the lymph nodes relative to the volume density in the lungs. Field emission scanning electron microscopy (FESEM) was used to examine MWCNT structure in the various tissues.

Results: Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively. Although agglomerates account for approximately 54% of lung burden, only singlet MWCNT were observed in the diaphragm, chest wall, liver, kidney, heart and brain. At one day post exposure, the average length of singlet MWCNT in liver and kidney, was comparable to that of singlet MWCNT in the lungs 8.2 ± 0.3 versus 7.5 ± 0.4 um, respectively. On average, there were 15,371 and 109,885 fibers per gram in liver, kidney, heart and brain at 1 day and 336 days post-exposure, respectively. The burden of singlet MWCNT in the lymph nodes, diaphragm, chest wall and extrapulmonary organs at 336 days post-exposure was significantly higher than at 1 day post-exposure.

Conclusions: Inhaled MWCNT, which deposit in the lungs, are transported to the parietal pleura, the respiratory musculature, liver, kidney, heart and brain in a singlet form and accumulate with time following exposure. The tracheobronchial lymph nodes contain high levels of MWCNT following exposure and further accumulate over nearly a year to levels that are a significant fraction of the lung burden 1 day post-exposure.

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Light and enhanced darkfield micrographs of MWCNTs detected in lavage of pleural space. The figure shows a comparison of the light and enhanced darkfield image of a singlet MWCNT in lavage of the pleural space in mice at 336 days post-exposure.
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Figure 4: Light and enhanced darkfield micrographs of MWCNTs detected in lavage of pleural space. The figure shows a comparison of the light and enhanced darkfield image of a singlet MWCNT in lavage of the pleural space in mice at 336 days post-exposure.

Mentions: Analysis demonstrated that singlet MWCNT were present in lavage of the pleural space from MWCNT-exposed mice at 336 days post-exposure. Figure 4 shows an example of same singlet MWCNT in the lavage fluid as visualized by light and enhanced darkfield microscopy. MWCNTs in the pleural lavage were singlets with an average length of 6.9 microns. Singlet MWCNTs in the lavage of the pleural space were found either in close contact or penetrating into the cytoplasm and/or nucleus of monocytes in the pleural lavage. There was approximately 1 singlet MWCNT per 3000 cells in the pleural lavage. This is comparable to the 1 crocidolite fiber per 4000 cells in pleural lavage reported for an inhalation exposure study of asbestos-induced pleural injury in rats [29]. Based on counting cytocentrifuge slides of the 1 ml pleural lavage fluid there was an average of 23.7 ± 7.6 (Mean ± S.E., N = 5) singlet MWCNT, in the lavage of the pleural space. Pleural lavage at 1 day post-exposure was not conducted.


Extrapulmonary transport of MWCNT following inhalation exposure.

Mercer RR, Scabilloni JF, Hubbs AF, Wang L, Battelli LA, McKinney W, Castranova V, Porter DW - Part Fibre Toxicol (2013)

Light and enhanced darkfield micrographs of MWCNTs detected in lavage of pleural space. The figure shows a comparison of the light and enhanced darkfield image of a singlet MWCNT in lavage of the pleural space in mice at 336 days post-exposure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750633&req=5

Figure 4: Light and enhanced darkfield micrographs of MWCNTs detected in lavage of pleural space. The figure shows a comparison of the light and enhanced darkfield image of a singlet MWCNT in lavage of the pleural space in mice at 336 days post-exposure.
Mentions: Analysis demonstrated that singlet MWCNT were present in lavage of the pleural space from MWCNT-exposed mice at 336 days post-exposure. Figure 4 shows an example of same singlet MWCNT in the lavage fluid as visualized by light and enhanced darkfield microscopy. MWCNTs in the pleural lavage were singlets with an average length of 6.9 microns. Singlet MWCNTs in the lavage of the pleural space were found either in close contact or penetrating into the cytoplasm and/or nucleus of monocytes in the pleural lavage. There was approximately 1 singlet MWCNT per 3000 cells in the pleural lavage. This is comparable to the 1 crocidolite fiber per 4000 cells in pleural lavage reported for an inhalation exposure study of asbestos-induced pleural injury in rats [29]. Based on counting cytocentrifuge slides of the 1 ml pleural lavage fluid there was an average of 23.7 ± 7.6 (Mean ± S.E., N = 5) singlet MWCNT, in the lavage of the pleural space. Pleural lavage at 1 day post-exposure was not conducted.

Bottom Line: Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively.The burden of singlet MWCNT in the lymph nodes, diaphragm, chest wall and extrapulmonary organs at 336 days post-exposure was significantly higher than at 1 day post-exposure.The tracheobronchial lymph nodes contain high levels of MWCNT following exposure and further accumulate over nearly a year to levels that are a significant fraction of the lung burden 1 day post-exposure.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Inhalation exposure studies of mice were conducted to determine if multi-walled carbon nanotubes (MWCNT) distribute to the tracheobronchial lymphatics, parietal pleura, respiratory musculature and/or extrapulmonary organs. Male C57BL/6 J mice were exposed in a whole-body inhalation system to a 5 mg/m3 MWCNT aerosol for 5 hours/day for 12 days (4 times/week for 3 weeks, lung burden 28.1 ug/lung). At 1 day and 336 days after the 12 day exposure period, mice were anesthetized and lungs, lymph nodes and extrapulmonary tissues were preserved by whole body vascular perfusion of paraformaldehyde while the lungs were inflated with air. Separate, clean-air control groups were studied at 1 day and 336 days post-exposure. Sirius Red stained sections from lung, tracheobronchial lymph nodes, diaphragm, chest wall, heart, brain, kidney and liver were analyzed. Enhanced darkfield microscopy and morphometric methods were used to detect and count MWCNT in tissue sections. Counts in tissue sections were expressed as number of MWCNT per g of tissue and as a percentage of total lung burden (Mean ± S.E., N = 8 mice per group). MWCNT burden in tracheobronchial lymph nodes was determined separately based on the volume density in the lymph nodes relative to the volume density in the lungs. Field emission scanning electron microscopy (FESEM) was used to examine MWCNT structure in the various tissues.

Results: Tracheobronchial lymph nodes were found to contain 1.08 and 7.34 percent of the lung burden at 1 day and 336 days post-exposure, respectively. Although agglomerates account for approximately 54% of lung burden, only singlet MWCNT were observed in the diaphragm, chest wall, liver, kidney, heart and brain. At one day post exposure, the average length of singlet MWCNT in liver and kidney, was comparable to that of singlet MWCNT in the lungs 8.2 ± 0.3 versus 7.5 ± 0.4 um, respectively. On average, there were 15,371 and 109,885 fibers per gram in liver, kidney, heart and brain at 1 day and 336 days post-exposure, respectively. The burden of singlet MWCNT in the lymph nodes, diaphragm, chest wall and extrapulmonary organs at 336 days post-exposure was significantly higher than at 1 day post-exposure.

Conclusions: Inhaled MWCNT, which deposit in the lungs, are transported to the parietal pleura, the respiratory musculature, liver, kidney, heart and brain in a singlet form and accumulate with time following exposure. The tracheobronchial lymph nodes contain high levels of MWCNT following exposure and further accumulate over nearly a year to levels that are a significant fraction of the lung burden 1 day post-exposure.

Show MeSH
Related in: MedlinePlus