Adsorption of Surfactant Lipids by Single-Walled Carbon Nanotubes in Mouse Lung upon Pharyngeal Aspiration

Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we ( 47 ) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique ( 2 ). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m3, 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5–20 μg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K- ras gene locus in the lung of C57BL/6 mice.

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00186.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. L87-L97 ◽

Cited By ~ 199

Author(s):

R. R. Mercer ◽

J. Scabilloni ◽

L. Wang ◽

E. Kisin ◽

A. R. Murray ◽

...

Keyword(s):

Carbon Nanotubes ◽

Connective Tissue ◽

Single Walled Carbon Nanotubes ◽

Tissue Response ◽

Mouse Lung ◽

Single Walled Carbon ◽

Inflammatory Phase ◽

Macrophage Phagocytosis ◽

Granulomatous Lesions ◽

Walled Carbon Nanotubes

Nanoparticles have a fundamental dimension of <100 nm. However, on 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), in which granulomatous lesions encased by epithelioid macrophages were produced by large agglomerates. In this study, we tested the hypothesis of whether 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 postexposure. Deposits were generally <1 μm. Macrophage phagocytosis of DSWCNT was rarely observed at any time point. Lung responses were studied by lavage and morphometry at 1 h, 1 day, 7 day, and 1 mo after a single DSWCNT exposure of 10 μg/mouse. Lung sections and lavage cells demonstrated an early, transient neutrophilic and inflammatory phase that 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 and 1-h, 1-day, 7-day, and 1-mo postexposure groups, respectively. The results demonstrate that dispersed SWCNT are rapidly incorporated into the alveolar interstitium and that they produce an increase in collagen deposition.

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