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Am J Physiol Lung Cell Mol Physiol (November 16, 2007). doi:10.1152/ajplung.00186.2007
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Submitted on May 10, 2007
Accepted on November 11, 2007

Alteration of deposition pattern and pulmonary response as a result of improved dispersion of aspirated single walled carbon nanotubes in a mouse model

Robert R. Mercer1*, James F. Scabilloni.1, Liying Wang2, Elena R. Kisin1, Ashley R. Murray1, Diane Schwegler-Berry1, Anna A. Shvedova1, and Vincent Castranova3

1 Physiology and Pathology Research Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States
2 PPRB, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States
3 Department of Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States

* To whom correspondence should be addressed. E-mail: RMercer{at}cdc.gov.

Nanoparticles have a fundamental dimension less than 100 nanometers. However, upon suspension in media agglomerates of nanoparticles are the more common structure. This is particularly evident in prior intratracheal instillation or aspiration studies of single walled carbon nanotubes (SWCNT) where granulomatous lesions encased by epithelioid macrophages were produced by large agglomerates. The hypothesis to be tested is that exposure to more dispersed SWCNT structures would alter pulmonary distribution and response. A dispersed preparation of single walled carbon nanotubes (DSWCNT) with a mean diameter of 0.69 µm was given by pharyngeal aspiration to C57BL/6 mice. Electron microscopy demonstrated a highly dispersed, interstitial distribution of DSWCNT deposits by 1 day post-exposure. Deposits were generally less than 1 micron. Macrophage phagocytosis of DSWCNT was rarely observed at any time point. Lung responses were studied by lavage and morphometry at 1 hour, 1 day, 7 day and 1 month after a single DSWCNT exposure of 10 µg/mouse. Lung sections and lavage cells demonstrated an early, transient neutrophilic, inflammatory phase which rapidly resolved and was similar to that observed with large agglomerates. No granulomatous lesions or epithelioid macrophages were detected. Morphometric measurement of Sirius Red staining was used to assess the connective tissue response. The average thickness of connective tissue in alveolar regions was 0.10±0.02, 0.09±0.02, 0.10±0.01, 0.48±0.04 and 0.88±0.19 µm for PBS, 1 hour, 1 day, 7 day and 1 month groups, respectively. The results demonstrate that dispersed SWCNT are rapidly incorporated into the alveolar interstitium and produce an increase in collagen deposition.




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