Pleural macrophage recruitment and activation in asbestos-induced pleural injury.

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/m3) or NIEHS chrysotile fibers (average concentration 8.51 mg/m3). 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-x) (by an enzyme-linked immunosorbent assay method). Significantly greater amounts of NO as well as TNF-a 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.

Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice

“…This response is consistent with the increase in inflammatory leukocytes observed in the pleural space in rats after pulmonary exposure to long asbestos fibres by both intratracheal instillation (Oberdoerster et al 1983) and inhalation (Choe et al 1997). Similar to the length-dependent response to CNT in the lungs, the inflammatory reaction in the pleural space was confined to the CNT sample containing long fibres: NT long .…”

Immune responses and immunotherapeutic interventions in malignant pleural mesothelioma

“…Inhaled asbestos fibers present within the lung cause infiltration of circulating macrophages into the pleural space, which try to phagocytose the inhaled foreign bodies [10]. In the effort to clear asbestos fibers, reactive oxygen species are generated, with subsequent production of inflammatory cytokines and increased recruitment of immune cells to sites of inflammation within the pleura [11-14]. Macrophages’ repeated phagocytotic efforts fail to clear the asbestos fibers, resulting in continued generation of reactive oxygen species and secretion of pro-inflammatory cytokines [14].…”

“…In the effort to clear asbestos fibers, reactive oxygen species are generated, with subsequent production of inflammatory cytokines and increased recruitment of immune cells to sites of inflammation within the pleura [11-14]. Macrophages’ repeated phagocytotic efforts fail to clear the asbestos fibers, resulting in continued generation of reactive oxygen species and secretion of pro-inflammatory cytokines [14]. This process, often referred to as “frustrated phagocytosis,” represents a chronic inflammatory state that has been shown to generate malignant transformation of mesothelial cells in vitro (Fig.…”

Molecular Pathways: Targeting Mechanisms of Asbestos and Erionite Carcinogenesis in Mesothelioma

“…The inflammatory infiltrate into tissue areas containing asbestos deposits consists largely of phagocytic macrophages that internalize asbestos and release numerous cytokines and mutagenic ROS (32). Among the cytokines secreted, tumor necrosis factor-α (TNF-α) and IL-1β have been convincingly linked to asbestos-related carcinogenesis (31, 33).…”