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Crocidolite Asbestos Fibers Undergo Size-dependent Microtubule-mediated Transport after Endocytosis in Vertebrate Lung Epithelial Cells¹

Wadsworth Center for Laboratories and Research, Albany, New York 12201-0509 [R. W. C., J. G. A., C. L. R.]; Department of Biology, Siena College, Loudenville, New York 12211 [J. H. H.]; and Department of Biomedical Sciences, State University of New York, Albany, New York 12222 [C. L. R.]

The large respiratory epithelial cells within primary cultures of newt (Taricha granulosa) lung are uniquely suited for high resolution video-enhanced light-microscopic studies. We show here that these cells incorporate crocidolite asbestos fibers within 18 h by endocytosis. Once inside the cell, fibers less than 5 µm in length are seen by video light microscopy to undergo saltatory transport at a maximum velocity of 1.18 µm/s. By contrast, fibers over 5 µm long rarely exhibit saltatory motion. Over time, all of the fibers become preferentially located near the nucleus. This perinuclear accumulation is largely inhibited by disassembling the cytoplasmic microtubules with nocodazole. Same cell correlative light and electron microscopy reveal that fibers exhibiting saltatory behavior are enclosed within a membrane. From these observations we conclude that, upon incorporation into epithelial cells, asbestos fibers undergo size-dependent active transport along cytoplasmic microtubules. Our data are the first to link the dimension-dependent transforming ability of asbestos fibers to a basic cellular function, i.e., the microtubule-dependent transport of cellular components.

¹ This work was supported by NIH GMS Grants R01-40198 (C. L. R.) and R15-41871 (J. H. H.), and by RR 01219, awarded by the National Center for Research Resources (Department of Health and Human Services/Public Health Service), to support the Wadsworth Center's Biological Microscopy and Image Reconstruction Facility as a National Biotechnological Resource.

² To whom requests for reprints should be addressed, at Wadsworth Center for Labs and Research, P. O. Box 509, Albany, NY 12201-0509.

Received 4/23/91. Accepted 7/ 8/91.

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