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Cytotoxicity of size-selected manville code 100 (JM-100) glass fibers on human alveolar macrophages.

Castranova-V; Zeidler-PC; Calhoun-WJ; Ameredes-BT; Clark-MP; Deye-G; Baron-P; Blake-T
Toxicologist 2003 Mar; 72(S-1):45
A previous study using rat alveolar macrophages (AMs) demonstrated that glass fibers > 17microm long were larger than these pneumocytes and resulted in frustrated phagocytosis, while fibers < 7microm long were completely engulfed. Frustrated phagocytosis was associated with a substantially greater cytotoxicity of long versus short fibers (Blake et al. J Toxicol Environ Health. Part A, 54:243, 1998). Human AMs are larger than rat AMs, approximately 18 and 13microm in diameter, respectively. Therefore, the objective of this study was to evaluate the cytotoxicity of fibers of different lengths on human AMs. JM-100 glass fiber samples of 8, 10, 16, and 20microm lengths were obtained by classification of airborne fibers by dielectrophoresis. Human AMs were obtained by segmental bronchoalveolar lavage of healthy, non-smoking volunteers. AMs were treated with three different doses (determined by fiber numbers) of the sized fiber samples for 18 hours in vitro. Cytotoxicity caused by the fiber samples was then determined by monitoring membrane damage (leak of lactate dehydrogenase [LDH]) and loss of function (decrease in zymosan-stimulated chemiluminescence [CL]). Microscopic analysis indicated that human AMs were large enough to completely engulf fibers which were 20microm long. All fiber length fractions tested exhibited equal cytotoxicity, i.e., increasing LDH and decreasing CL in the same dose-dependent fashion. The data indicate that because human AMs are larger than rat AMs they are able to phagocytize longer fibers and the absence of frustrated phagocytosis results in lower fiber toxicity in human AMs. These differences in the AM response to long fibers between human and rat phagocytes should be considered when designing in vivo exposures using the rat model.
Laboratory-animals; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disease; Lung-fibrosis; Man-made-mineral-fibers; Glass-products; Glass-wool; Fibrous-dusts; Fibrous-glass; Cytotoxic-effects
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Research Tools and Approaches: Exposure Assessment Methods
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The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah