Asbestos exposure induces MCP-1 secretion by pleural mesothelial cells

We showed previously that both crocidolite and chrysotile asbestos inhalati on induced a persistent macrophage inflammatory response within the pleural space of the rat. We postulated that the stimulus for pleural macrophage r ecruitment after asbestos exposure was the induction of monocyte chemoattra ctant protein-1 (MCP-1) synthesis by pleural mesothelial cells. To test thi s hypothesis, rat pleural mesothelial cells (RPMC) were cultured with or wi thout chrysotile or crocidolite asbestos fibers (8 mu g/cm(2)) in the prese nce (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 R T-PCR in RPMC cultured for 2 to 24 hours, and MCP-1 protein secretion was m easured by ELISA in conditioned medium from 24-hour and 48-hour cultures. C rocidolite and chrysotile fibers induced MCP-1 mRNA expression in RPMC whic h was maximal after 12 hours in the absence of cytokines, but which peaked after 2 hours when RPMC mere challenged with asbestos + TNF-alpha or IL-1 b eta. Both types of asbestos also significantly increased MCP-1 protein secr etion after 24 and 48 hours (P < .0001), an effect that was potentiated by cytokine stimulation. Rats exposed by inhalation to either chrysotile or cr ocidolite asbestos fibers also had greater amounts of MCP-1 protein in thei r pleural lavage fluid than did sham-exposed rats. These findings suggest t hat MCP-1 secretion by RPMC may have a role in the initiation and/or potent iation of asbestos-induced pleural injury.