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Carbon nanotubes are shaped like fibres and can stimulate inflammation at the surface of the peritoneum when injected into the abdominal cavity of mice, raising concerns that inhaled nanotubes may cause pleural fibrosis and/or mesothelioma. Here, we show that multiwalled carbon nanotubes reach the subpleura in mice after a single inhalation exposure of 30 mg m(-3) for 6 h. Nanotubes were embedded in the subpleural wall and within subpleural macrophages. Mononuclear cell aggregates on the pleural surface increased in number and size after 1 day and nanotube-containing macrophages were observed within these foci. Subpleural fibrosis unique to this form of nanotubes increased after 2 and 6 weeks following inhalation. None of these effects was seen in mice that inhaled carbon black nanoparticles or a lower dose of nanotubes (1 mg m(-3)). This work suggests that minimizing inhalation of nanotubes during handling is prudent until further long-term assessments are conducted.

Pleural inflammation is a sequela of exposure to toxic mineral fibers such as amosite asbestos. This inflammatory response involves the influx of leukocytes from the vasculature into the pleural space. Adhesion molecules such as intercellular adhesion molecule-1 (ICAM)-1 and chemokines such as monocyte chemoattractant protein-1 (MCP)-1 and macrophage inhibitory protein-2 (MIP)-2 are known to be important in pulmonary inflammation following inhalation of particulate matter. However, little is known about their role in pleural inflammation secondary to amosite asbestos exposure. Because the pleural mesothelial cell is believed to be a key target cell of asbestos exposure, the purpose of this study was to determine if ICAM-1, MCP-1, and MIP-2 proteins were secreted by these mesothelial cells following in vitro and in vivo exposure to amosite asbestos. Increased levels of ICAM-1 and MCP-1 protein were measured following 24 or 48 hours exposure of cultured rat pleural mesothelial cells to amosite fibers (1.5 to 5.0 micro g/cm(2)). Increased levels of ICAM-1, MCP-1, and MIP-2 protein were found in pleural lavage fluid from Fischer-344 rats exposed to amosite asbestos for 4 and 12 weeks and after a 12-week recovery period (following the 12-week exposure period). These findings suggest that the secretion of ICAM-1, MCP-1, and MIP-2 by rat pleural mesothelial cells may contribute to amosite-induced pleural inflammation.

Interspecies differences in pulmonary and pleural responses to the inhalation of natural mineral and synthetic vitreous fibers have been observed in chronic and subchronic studies. However, the reasons for these differences are not clearly understood. There are also fiber-specific differences in the outcome of chronic inhalation exposure to natural mineral and synthetic vitreous fibers. Whether these differences are dependent upon the ability of these fibers to translocate to the pleural space is unknown. The present study was conducted to compare retained fiber burdens and selected pathological responses in the pleural compartments of rats and hamsters following subchronic inhalation of MMVF 10a fiberglass, a fiber negative for tumorigenesis or fibrosis in chronic studies. Fischer 344 rats and Syrian golden hamsters were exposed for 4 or 12 weeks by nose-only inhalation at nominal aerosol mass concentrations of 45 mg/m3 (610 WHO fibers/cc). Pulmonary fiber burdens and pulmonary inflammatory responses were greater in rats than in hamsters. The total number of fibers in the lung was approximately three orders of magnitude greater than in the pleural compartment. Pleural burdens in the hamster (160 fibers/cm2 surface area) were significantly greater than burdens in similarly exposed rats (60 fibers/cm2 surface area) following 12 weeks of exposure. With time postexposure, pleural burdens decreased in hamsters but were essentially unchanged in rats. Pleural inflammatory responses in both species were minimal. In rats, pleural inflammation was characterized by increased numbers of macrophages and increases in mesothelial cell replication during the period of fiber exposure. In contrast, hamsters had increased numbers of macrophages and lymphocytes, and mesothelial-cell replication indices were elevated on the parietal pleura of the costal wall and diaphragm, with some of these responses persisting through 12 weeks of postexposure recovery. Taken together, the results suggest that differences among rodent species in pleural responses to inhaled fibers are due to a delivered dose of fibers and to the biological responses to the presence of the fibers.

The pleura is a target site for toxic effects induced by a variety of fibrous particulates, including both natural mineral and man made vitreous fibers. We examined selected cytological and bio chemical indicators of inflammation in both the pleural compart ment and pulmonary parenchyma in F344 rats following inhala tion of RCF-1, a kaolin-based ceramic fiber. Male F344 rats were exposed by Inhalation to 89 mg/m3 (2645 WHO fibers/cc) RCF-1 6 hr/day for 5 consecutive days. In lung parenchyma, cytological and biochemical inflammatory responses occurred rapidly following exposure. In contrast, pleural responses were delayed in onset and of a much smaller magnitude than those observed in lung. At both Day 1 and Day 28 postexposure, increased quantities of lactate dehydrogenase, N-acetyl glucosaminidase, alkaline phosphatase, albumin, and neutrophils were present in bronchoalveolar lavage fluid. These responses were attenuated at the latter time point. No significant responses were detected in pleural lavage fluid until 28 days following exposure, at which time elevated numbers of macrophages and eosinophils, but not neutrophils, were observed. Increased albumin and fibronectin were also ob served in PLF at this latter time point. These findings demonstrate that the onset of pleural and pulmonary responses following inhalation of RCF-1 are temporally separated and that pleural injury may increase in severity with time following exposure. The increase in severity of pleural inflammation found in the postexposure period cannot be readily explained by fiber translocation. [ABSTRACT FROM AUTHOR]