Environmental Health Perspectives 105, Supplement 5, September 1997

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Pleural Macrophage Recruitment and Activation in Asbestos-induced Pleural Injury

Nonghoon Choe, 1 Shogo Tanaka, 1 Weijia Xia, 1 David R. Hemenway, 2 Victor L. Roggli, 3 and Elliott Kagan 1

1 Department of Pathology, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, Maryland
2 Department of Civil and Environmental Engineering, University of Vermont, Burlington, Vermont
3 Department of Pathology, Duke University Medical Center, Durham, North Carolina

Abstract
The pathogenesis of asbestos-induced pleural fibrosis is poorly understood. Moreover, there has been a long-standing controversy regarding the relative potential of different commercial types of asbestos to cause pleural disease. We postulated that inhaled asbestos fibers translocate to the pleural space where they stimulate the recruitment and activation of pleural macrophages. To test this hypothesis, and to determine whether there are differences between inhaled amphibole and serpentine asbestos, Fischer 344 rats were exposed by intermittent inhalation (6 hr/day for 5 days/week over 2 weeks) to either National Institute of Environmental Health Sciences (NIEHS) crocidolite (average concentration 7.55 mg/m 3 ) or NIEHS chrysotile fibers (average concentration 8.51 mg/m 3 ). Comparisons were made with sham-exposed rats. The rats were sacrificed at 1 and 6 weeks after the cessation of exposure. More pleural macrophages were recovered at 1 and 6 weeks after crocidolite and chrysotile exposure than after sham exposure. Small numbers of crocidolite fibers (approximately 1 per 4000 cells) were detected in the pleural cell pellet of one crocidolite-exposed rat by scanning electron microscopy. Pleural macrophage supernatants were assayed for production of nitric oxide (NO) (by the Griess reaction) and tumor necrosis factor alpha (TNF- alpha ) (by an enzyme-linked immunosorbent assay method). Significantly greater amounts of NO as well as TNF- alpha were generated by pleural macrophages at 1 and 6 weeks after either crocidolite or chrysotile inhalation than after sham exposure. Conceivably, translocation of asbestos fibers to the pleural space may provide a stimulus for persistent pleural space inflammation, cytokine production, and the generation of toxic oxygen and nitrogen radicals. Enhanced cytokine secretion within the pleural space may in turn upregulate adhesion molecule expression and the synthesis of extracellular matrix constituents by pleural mesothelial cells. Thus, our findings may have significance for the development of asbestos-induced pleural injury. -- Environ Health Perspect 105(Suppl 5):1257-1260 (1997)

Key words : asbestos, pleural fibrosis, pleural macrophage, tumor necrosis factor alpha, nitric oxide, cytokines

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 16 April 1997.

This study was supported by grants from the National Institutes of Health (HL-54196) and the Asbestos Victims Special Fund Trust, a charitable organization exempt from federal taxation under Section 501(c)(3) of the Internal Revenue Code. The contents of this article do not necessarily reflect the views of the Asbestos Victims Special Fund Trust or the parties that support it.

Address correspondence to Dr. E. Kagan, Department of Pathology, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, 4301 Jones Bridge Road, Bethesda, MD 20814-4799. Telephone: (301) 295-3492. Fax: (301) 295-1640. E-mail: ekagan@usuhs.mil

Abbreviations used: DMEM, Dulbecco modified Eagle medium; EDXA, energy-dispersive X-ray analysis; HBSS, Hanks balanced salt solution; NIEHS, National Institute of Environmental Health Sciences; NO, nitric oxide; SEM, scanning electron microscopy; TNF- alpha , tumor necrosis factor alpha.

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Last Update: October 30, 1997