Soluble Icam-1, McP-1, and Mip-2 Protein Secretion by Rat Pleural Mesothelial Cells Following Exposure to Amosite Asbestos

Abstract

Pleural inflammation is a sequela of exposure to toxic mineral fibers such as amosite asbestos. This inflammatory response involves the influx of leukocytes from the vasculature into the pleural space. Adhesion molecules such as intercellular adhesion molecule-1 (ICAM)-1 and chemokines such as monocyte chemoattractant protein-1 (MCP)-1 and macrophage inhibitory protein-2 (MIP)-2 are known to be important in pulmonary inflammation following inhalation of particulate matter. However, little is known about their role in pleural inflammation secondary to amosite asbestos exposure. Because the pleural mesothelial cell is believed to be a key target cell of asbestos exposure, the purpose of this study was to determine if ICAM-1, MCP-1, and MIP-2 proteins were secreted by these mesothelial cells following in vitro and in vivo exposure to amosite asbestos. Increased levels of ICAM-1 and MCP-1 protein were measured following 24 or 48 hours exposure of cultured rat pleural mesothelial cells to amosite fibers (1.5 to 5.0 micro g/cm(2)). Increased levels of ICAM-1, MCP-1, and MIP-2 protein were found in pleural lavage fluid from Fischer-344 rats exposed to amosite asbestos for 4 and 12 weeks and after a 12-week recovery period (following the 12-week exposure period). These findings suggest that the secretion of ICAM-1, MCP-1, and MIP-2 by rat pleural mesothelial cells may contribute to amosite-induced pleural inflammation.

Effects of nano particles on antigen-related airway inflammation in mice

“…MCP-1 also plays a role in recruitment of eosinophils to acute and chronic inflammatory sites [36]. Furthermore, some particles such as silica [37] and amosite asbestos [38] reportedly can induce MCP-1 in vitro and in vivo . Thus, our findings indicate that pulmonary exposure to carbon nano particles may induce MCP-1 expression in the airways.…”

Nickel Nanoparticles Enhance Platelet-Derived Growth Factor–Induced Chemokine Expression by Mesothelial Cells via Prolonged Mitogen-Activated Protein Kinase Activation

“…Pleural mesothelial cells are another source for increased levels of PDGF-BB after asbestos exposure and injury. This suggests that PDGF-BB could act in an autocrine fashion to increase CCL2 expression in mesothelial cells (18,19). We have previously shown that macrophages engulf inhaled MWCNTs and then migrate to the pleura, where they accumulate beneath the mesothelium (8).…”

“…CCL2 is considered to be a profibrotic chemokine, as it plays a role in stimulating fibroblasts to produce collagen by induction and activation of TGF-b1 (20). In addition, CCL2 is a potent chemoattractant produced by pleural mesothelial cells that induces the migration of macrophages to an area of inflammation and injury (19). Time course experiments demonstrated that CCL2 mRNA and protein were induced transiently by PDGF-BB, whereas NiNPs caused a sustained increase in CCL2 expression ( Figures E1 and E2).…”

“…For example, PDGF increases the production of CCL2 (monocyte chemoattractant protein [MCP]-1), a profibrogenic and proangiogenic chemokine, via a mechanism involving the activation of phosphoinositide 3-kinase and NF-kB in NIH/3T3 fibroblasts (16,17). Rat pleural mesothelial cells also produce CCL2 in response to asbestos fibers in vitro, which, in turn, serves as a potent chemoattractant for monocytes and macrophages (18,19). CCL2 stimulates fibroblasts to produce TGF-b1 and collagen (20).…”

The Role of Inflammation in Development and Therapy of Malignant Mesothelioma

“…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). Recent studies from our group have also shown that human mesothelial cells acquire resistance to asbestos-induced toxicity via induction of one or more Epidermal Growth Factor Receptor (EGFR)-linked survival pathways (PI3K/AKT/ERK1/2) during Simian Virus 40 (SV40) transformation and carcinogenesis (Shukla et al, 2011).…”