PLEURAL MACROPHAGE RECRUITMENT AND ACTIVATION IN ASBESTOS-INDUCED PLEURAL INJURY

The pathogenesis of asbestos-induced pleural fibrosis is poorly unders tood Moreover, there has been a long-standing controversy regarding th e relative potential of different commercial types of asbestos to caus e pleural disease. We postulated that inhaled asbestos fibers transloc ate to the pleural space where they stimulate the recruitment and acti vation of pleural macrophages. To test this hypothesis, and to determi ne whether there are differences between inhaled amphibole and serpent ine 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 concentr ation 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 cr ocidolite fibers (approximately 1 per 4000 cells) were detected ii? th e pleural cell pellet of one crocidolite-exposed rat by scanning elect ron microscopy. Pleural macrophage supernatants were assayed for produ ction of nitric oxide (NO) (by the Griess reaction) and tumor necrosis factor alpha (TNF-alpha) (by an enzyme-linked immunosorbent assay met hod). Significantly greater amounts of NO as well as TNF-alpha were ge nerated by pleural macrophages at 1 and 6 weeks after either crocidoli te or chrysotile inhalation than after sham exposure. Conceivably, tra nslocation of asbestos fibers to the pleural space may provide a stimu lus for persistent pleural space inflammation, cytokine production, an d the generation of toxic oxygen and nitrogen radicals. Enhanced cytok ine secretion within the pleural space may in turn upregulate adhesion molecule expression and the synthesis of extracellular matrix constit uents by pleural mesothelial cells. Thus, our findings may have signif icance for the development of asbestos-induced pleural injury.