Environmental Health Perspectives 105, Supplement 5, September 1997

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Silica-induced Apoptosis in Alveolar and Granulomatous Cells in Vivo

James Leigh, 1 He Wang, 2 Antonio Bonin, 1 Matthew Peters, 2 and Xiuyao Ruan 2

1 National Institute of Occupational Health and Safety, Sydney, NSW, Australia
2 University of Sydney, Sydney, NSW, Australia

Abstract
Silica is a toxicant that can stimulate cells to produce various cellular products such as free radicals, cytokines, and growth factors. Silica and its induced substances may induce apoptosis to regulate the evolution of silica-induced inflammation and fibrosis. To examine this hypothesis, groups of Wistar male rats were intratracheally instilled with different doses of Min-U-Sil 5 silica (Silica, Berkeley Springs, WV). Ten days after the instillation, we obtained cells by bronchoalveolar lavage and placed them on slides by cytospin preparation. The slides were stained with Diff-Quik (Lab Aids, Sydney, NSW, Australia) and examined under oil immersion. A substantial number of cells with apoptotic features were identified in all silica-instilled rats and the apoptosis was confirmed by agarose gel electrophoresis. The number of apoptotic cells was clearly related to silica dosage. Engulfment of apoptotic cells by macrophages was also noted. Neutrophil influx in silica-instilled rats could be saturated with the increase of silica dosage and the number of macrophages in different dose groups changed in parallel with the proportion of apoptotic cells. Fifty-six days after instillation, morphologically apoptotic cells could be identified in granulomatous cells of lung tissue from silica-instilled rats. We conclude that intratracheal instillation of silica could induce apoptosis in both alveolar and granulomatous cells, and the apoptotic change and subsequent engulfment by macrophages might play a role in the evolution of silica-induced effects. -- Environ Health Perspect 105(Suppl 5):1241-1245 (1997)

Key words : silica, dust, apoptosis, lung, inflammation, fibrosis, leukocytes, granuloma, bronchoalveolar lavage

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 31 March 1997.

Address correspondence to Dr. J. Leigh, National Institute of Occupational Health and Safety, GPO Box 58, Sydney, NSW 2001 Australia. Telephone: 612 9577 9303. Fax: 612 9577 9300. E-mail: jleigh@worksafe.gov.au

Abbreviations used: BAL, bronchoalveolar lavage; LDH, lactate dehydrogenase; TNF, tumor necrosis factor; TGF, transforming growth factor.

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Last Update: November 16, 1997