Asbestos exposure induces MCP-1 secretion by pleural mesothelial cells

We showed previously that both crocidolite and chrysotile asbestos inhalation induced a persistent macrophage inflammatory response within the pleural space of the rat. We postulated that the stimulus for pleural macrophage recruitment after asbestos exposure was the induction of monocyte chemoattractant protein-1 (MCP-1) synthesis by pleural mesothelial cells. To test this hypothesis, rat pleural mesothelial cells (RPMC) were cultured with or without chrysotile or crocidolite asbestos fibers (8 micrograms/cm2) in the presence (50 ng/mL) or absence of either tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). MCP-1 mRNA expression was assessed by RT-PCR in RPMC cultured for 2 to 24 hours, and MCP-1 protein secretion was measured by ELISA in conditioned medium from 24-hour and 48-hour cultures. Crocidolite and chrysotile fibers induced MCP-1 mRNA expression in RPMC which was maximal after 12 hours in the absence of cytokines, but which peaked after 2 hours when RPMC were challenged with asbestos + TNF-alpha or IL-1 beta. Both types of asbestos also significantly increased MCP-1 protein secretion after 24 and 48 hours (P < .0001), an effect that was potentiated by cytokine stimulation. Rats exposed by inhalation to either chrysotile or crocidolite asbestos fibers also had greater amounts of MCP-1 protein in their pleural lavage fluid than did sham-exposed rats. These findings suggest that MCP-1 secretion by RPMC may have a role in the initiation and/or potentiation of asbestos-induced pleural injury.     

KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid after intratracheal asbestos

Mesothelial cells proliferate soon after asbestos deposition in the lung. The present study investigates whether the known mesothelial cell mitogens keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are present in the lung and specifically in the pleural cavity during the phase of mesothelial cell growth. Rats received 1 mg crocidolite asbestos in 0.5 mL water by intratracheal instillation and were killed up to 2 weeks later; tritiated thymidine was injected 1 hour before death. Bronchoalveolar lavage (BAL) and pleural lavage (PLL) were performed. Increased inflammatory cell numbers and protein levels were found in BAL but also in PLL at 1 day after asbestos deposition. In lung sections, labeling of mesothelial cells increased > 10-fold at day 1 and stayed above normal for 1 week. During this period, the levels of HGF and KGF were significantly raised in both BAL and PLL fluids. The PLL fluid had mitogenic activity for mesothelial cells in culture and this effect was significantly reduced by antibodies to HGF and KGF. The results indicate that fiber deposition in the airspaces rapidly induces lung injury and inflammation, in which growth factors for mesothelial cells KGF and HGF are secreted. These factors reach the pleural cavity at the time when mesothelial cell proliferation occurs. It is possible that the activated, dividing mesothelial population may then be more susceptible to DNA damage by any translocated fibers.     

Benign asbestos pleural diseases

The global incidence of asbestos-related lung diseases is expected to continue to rise. Although much attention is devoted to malignant diseases induced by asbestos, benign asbestos pleural diseases (pleural plaques, benign asbestos-related pleural effusion, diffuse pleural thickening, and rounded atelectasis) are common in clinical practice and often produce diagnostic difficulties. The authors describe the clinical features of benign asbestos-related pleural disease, before focusing on recent advances in radiology and on controversies surrounding the pathogenesis of asbestos-induced pleural injury. Advances in computed tomography have assisted the understanding and diagnosis of these diseases, and increasing evidence suggests radiologic appearances on computed tomography can predict impairment in pulmonary function tests. The pathogenesis of asbestos-induced pleural diseases has also been subject to extensive investigation. Asbestos fibers can provoke pleural inflammation from direct toxicity to mesothelial cells. Inhaled asbestos fibers can also elicit pleural injury indirectly via the release of growth factors and inflammatory cytokines from within the lung. Although progress has been made in the understanding of the mechanisms of asbestos pleural injury, many important questions remain unanswered. The role of genetic factors and possible environmental cofactors (eg, simian virus 40) in the pathogenesis of benign asbestos pleural diseases requires further research.