MCP-1 in pleural injury: CCR2 mediates haptotaxis of pleural mesothelial cells

Pleural injury results in the death of mesothelial cells and denudation of the mesothelial basement membrane. Repair of the mesothelium without fibros is requires proliferation and migration of mesothelial cells into the injur ed area. We hypothesized that monocyte chemoattractant:protein-l (MCP-1) in duces proliferative and haptotactic responses in pleural mesothelial cells (PMCs) and that the MCP-I binding receptor CCR2 mediates the pleural repair process.:We demonstrate that PMCs exhibited MCP-1-specific immunostaining on injury. MCP-1 induced proliferative and haptotactic responses in PMCs. P MCs express CCR2 in a time-dependent manner. Fluorescence-activated cell so rting analysis demonstrated that interleukin (IL)-2 upregulated CCR2 protei n expression in PMCs, whereas lipopolysaccharide (LPS) downregulated the re sponse at the initial period:compared with that in resting PMCs. However, t he inhibitory,potential of LPS was lost after 12 h and showed a similar res ponse at 24 and 48 h. Haptotactic migration was upregulated in PMCs that we re cultured in the presence of IL-2. The increased haptotactic capacity of mesothelial cells in the: presence of IL-2 correlated with increased CCRS m RNA:expression. PMCs cultured in the presence of LPS showed decreased hapto tactic activity to MCP-1. Blocking the CCR2 with neutralizing antibodies de creased the haptotactic response of PMCs to MCP-1. These results suggest th at the haptotactic migration of mesothelial cells in response to MCP-1 are mediated through CCR2, which may play a crucial role in reepithelialization of the denuded basement membrane at the site of pleural injury and may thu s contribute to the regeneration of the mesothelium during the process of p leural repair.