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-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.

TNF-α inhibits asbestos-induced cytotoxicity via a NF-κB-dependent pathway, a possible mechanism for asbestos-induced oncogenesis

“…Macrophages phagocytize asbestos but are unable to ''digest'' these fibers. Possibly because they are damaged by asbestos, these macrophages release TNF-␣ (prevalently) and other cytokines (8,12). TNF-␣ can also be released by HM, for example, when these cells are stimulated with erythromycin (38) or by crocidolite as shown here.…”

“…In animal models, asbestos induces the expression of monocyte chemoattractant protein-1 by mesothelial cells. Monocyte chemoattractant protein-1 expression favors the macrophage inflammatory response within the pleural space that follows asbestos exposure (12,15). Macrophages phagocytize asbestos but are unable to ''digest'' these fibers.…”

“…3 and 4). Upon differentiation into macrophages, these cells phagocytize asbestos and, in response, release numerous cytokines and reactive oxygen species that are mutagenic (8)(9)(10)(11)(12)(13)(14)(15). Among these cytokines, TNF-␣ has been linked to asbestos pathogenesis, although the mechanisms underlying this effect are unclear (15)(16)(17)(18).…”

Comparative Study of Toxic Effects of Anatase and Rutile Type Nanosized Titanium Dioxide Particles in vivo and in vitro

“…Also, MIP1a, secreted from rnTiO 2 burden alveolar macrophages, is possibly involved in the promotion of lung carcinogenesis (Xu et al, 2010). Similarly, pleural macrophage recruitment and activation are involved in the pathogenesis of asbestos (Choe et al, 1997). These results indicate two contrasting roles of alveolar macrophages in pathogenesis and host defense.…”

The Role of Inflammation in Development and Therapy of Malignant Mesothelioma

“…As discussed below, there are numerous studies supporting the concept that there is an inflammatory reaction following asbestos exposure (Choe et al, 1997). Hill et al (2003) reported that amosite asbestos causes pleural inflammation by increased secretion of Intercellular Adhesion Molecule-1 (ICAM-1), Monocyte Chemoattractant Protein-1 (MCP-1) and Macrophage Inhibitory Protein-2 (MIP-2) in pleural lavage fluid as well as in vitro mesothelial cell culture (Hill et al, 2003).…”