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Toxicologic Pathology
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Articles

Translocation Pathway of the Intratracheally Instilled C60 Fullerene from the Lung into the Blood Circulation in the Mouse: Possible Association of Diffusion and Caveolae-mediated Pinocytosis

Misaki Naota1
Akinori Shimada1
Takehito Morita1
Kenichiro Inoue2
Hirohisa Takano2

1 Department of Veterinary Pathology, Tottori University, Tottori, Japan
2 National Institute for Environmental Studies, Tsukuba, Japan

Correspondence: Misaki Naota, Department of Veterinary Pathology, Tottori University, Minami 4-101, Koyama, Tottori-shi, Tottori 680-8553, Japan; e-mail:misaki-naota{at}hotmail.co.jp.

Ultrafine particles are ubiquitous in ambient urban and indoor air from multiple sources and may contribute to adverse respiratory and cardiovascular diseases. Recently, it has been demonstrated that ultrafine particles (UFPs) are translocated from the lung into the systemic circulation. The exact pathway, however, for the translocation in the lung remains unclear. In this study, we examined the translocation pathway of intratracheally instilled C60 fullerene particles from the lung into the blood circulation in the mouse. Using light microscopy, aggregated particles of fullerene were observed in the capillary lumen in the lung and the pulmonary lymph nodes immediately after instillation. Electron microscopic analysis demonstrated an increased number of pinocytotic vesicles (caveolae) of various sizes in the type 1 alveolar epithelial cells (AEC) and endothelial cells; occasional caveolae containing some particulate substances were observed. In addition, particles of various sizes were observed throughout the structure of the air-blood barrier (ABB). These findings suggest that fullerene particles may pass the ABB by both diffusion and caveolae-mediated pinocytosis, resulting in immediate translocation into the systemic circulation.

Key Words: air-blood barrier • caveolae • C60 fullerene particles • diffusion • electron microscopy • mouse • translocation

Abbreviations: ABB, air-blood barrier; • AEC, alveolar epithelial cells; • PBS, phosphate-buffered saline; • UFPs, ultrafine particles.

This version was published on June 1, 2009

Toxicologic Pathology, Vol. 37, No. 4, 456-462 (2009)
DOI: 10.1177/0192623309335059


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