ASBESTOS-INDUCED PLEURAL DISEASE - 09/09/11
Résumé |
Asbestos, for unknown reasons, has an unusual affinity for the pleura. The manifestations of asbestos-induced pleural disease are multiple and varied, from effusion to fibrosis to malignancy. Certain types of pleural disease, such as pleural plaques, are nearly specific for asbestos exposure, whereas others, such as asbestos-induced pleural effusion, are difficult to identify unequivocally as asbestos-related. Although much progress on the basic mechanisms of asbestos-cellular interactions has been achieved, the origin of pleural disorders remains unknown. Furthermore, the relationship of the different pleural conditions with each other and with the pulmonary manifestations of asbestosis and lung cancer are not understood. In this article, we attempt to concentrate on the newer studies that offer answers to some of the questions above. We refer readers to recent reviews on asbestos-related pleural disease.26, 32, 43, 52
Asbestos has had significant value as a durable, fireproof material that could be woven. From the time of the ancient Greeks until the time of its peak use in the United States in the 1930s to 1960s, the variety of its applications has been astonishing.2 Although its use plummeted with the recognition of an association first with asbestosis and then with mesothelioma, asbestos is a vital material, still mined for applications particularly involving fire safety. Although asbestos is being replaced by man-made fibers such as fiberglass whenever possible, in some applications, it cannot be replaced. Understanding the mechanism of asbestos toxicity may allow us to avoid the same features that may be present in replacement fibers.
Asbestos, a commercial term describing fibrous, hydrated silicates, is categorized into two main families, the amphibole and the serpentine.59 Amphiboles are rigid fibers, sharp and highly resistant to chemical or biologic dissolution. There are five members: two commercially useful ones, crocidolite and amosite; and three noncommercial fibers that can be found as contaminants in other mining operations, tremolite, anthophyllite, and actinolite. Serpentine fibers are curly, easily shred into finer particles, and subject to dissolution in tissues; the only serpentine fiber is chrysotile. Much interest has centered on possible differences in toxicity between the two types of fibers, probably because 80% to 90% of commercially used asbestos is chrysotile. Generally, amphiboles are viewed as more toxic than the serpentine, with a closer association with many pleural diseases, particularly mesothelioma. Nevertheless, in in vitro studies, toxicities of serpentine and amphibole asbestos are similar, and in animal studies, chrysotile can readily induce tumors. Therefore, the greater apparent toxicity of amphibole asbestos in humans may be caused by its greater longevity in biologic tissues. Longer lasting fibers may well produce more disease, especially in the diseases such as mesothelioma with the longest latency period (30-40 years).
The toxic features of asbestos are still unknown but may lie in the shape, chemical composition, or surface structure of the fibers. The long, thin shape of the fiber was originally identified by Stanton and associates68 as a major determinant of its malignant potential, leading to the hypothesis that fibers more than 8 microns in length and less than 0.25 microns in width were toxic, regardless of their chemical composition. The shape may be important for the dispersal of fibers into the air, the migration of fibers in tissues once inhaled, or the trapping of fibers at the parietal pleural lymphatic stomata.38 Once engulfed by a cell, longer fibers may be more toxic than shorter fibers because of their interference with the cell cytoskeleton or because of their interference with chromosomes and the mitotic spindle during mitosis.34, 76 Although shape is important, chemical composition also contributes to the pathologic potential of asbestos. Chemical composition, particularly the presence of iron, determines the ability of the fiber to generate reactive oxygen species,30 and the chemical composition accounts for the biopersistence of fibers in tissues. Finally, surface characteristics may be important, as the surface determines how a fiber contacts its environment. By virtue of its positive surface charge, chrysotile, but not crocidolite, can interact with negatively charged sialic acid residues on cell membranes, leading to hemolysis.15 The surface also determines the materials that adsorb to the fiber in the biologic environment. Different biologic materials, including surfactant proteins and lipids, antibodies, adhesive extracellular matrix proteins such as vitronectin, and even DNA have been shown to bind onto the asbestos surface. These biologic materials allow the fibers to interact with cells, even permitting functional recognition by certain receptors such as integrins, leading to increased fiber uptake. 12 The surface coating may help explain differences in toxicity of the two main fiber families; for example, crocidolite, with a negative surface charge, and chrysotile, with a positive charge, adsorb different proteins.21 The overall toxicity of asbestos appears to be caused by a combination of its shape, chemical composition, and surface characteristics.
It is not known whether pleural disease is caused by asbestos fibers located in the lung or in the pleural tissues. Fibers in the lung may affect the adjacent pleura by way of cytokines derived from asbestos-exposed macrophages or from other cells. These cytokines may lead to proliferative and fibrotic effects, particularly of the visceral pleura. Although products from the lung may contribute to pleural disease, however, they alone are unlikely to account for the variety of pleural diseases or to explain the selectivity of asbestos for the pleural space. It is now known that asbestos can accumulate in the parietal pleural tissue to fiber counts higher than in the lung (see below). It appears more likely that these pleural fibers play an important etiologic role in pleural diseases, especially those diseases such as pleural plaques and mesothelioma that arise in the parietal, not the visceral, pleura. The cellular target of pleural fibers may include subpleural progenitor cells, pleural macrophages, or the pleural mesothelial cell. In in vitro studies, there is much evidence for direct effects of asbestos on mesothelial cells; asbestos-exposed mesothelial cells produce a range of cytokines and growth factors, sustain DNA and chromosomal damage, and can undergo cell death by apoptosis.14, 31, 40 Although the direct effects of fibers on mesothelial cells in vivo have been more difficult to demonstrate, asbestos fibers can be identified within pleural mesothelial cells in situ.19, 41 In summary, the relative contribution of pleural or lung fibers to the development of each of the asbestos-related pleural diseases is not known.
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| Address reprint requests to Stephen L. Nishimura, MD, Lung Biology Center, Building 1, Room 150, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110 This work was supported by Grants EHS06331 from the National Institutes of Health to V.C.B. and KO8 CA63148 to S.L.N. |
Vol 19 - N° 2
P. 311-329 - juin 1998 Retour au numéro
Article précédent
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