title: MCP-1 in pleural injury: CCR2 mediates haptotaxis of pleural mesothelial cells.
abstract: Pleural injury results in the death of mesothelial cells and denudation of the mesothelial basement membrane. Repair of the mesothelium without fibrosis requires proliferation and migration of mesothelial cells into the injured area. We hypothesized that monocyte chemoattractant protein-1 (MCP-1) induces proliferative and haptotactic responses in pleural mesothelial cells (PMCs) and that the MCP-1 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. PMCs express CCR2 in a time-dependent manner. Fluorescence-activated cell sorting analysis demonstrated that interleukin (IL)-2 upregulated CCR2 protein expression in PMCs, whereas lipopolysaccharide (LPS) downregulated the response at the initial period compared with that in resting PMCs. However, the inhibitory potential of LPS was lost after 12 h and showed a similar response at 24 and 48 h. Haptotactic migration was upregulated in PMCs that were cultured in the presence of IL-2. The increased haptotactic capacity of mesothelial cells in the presence of IL-2 correlated with increased CCR2 mRNA expression. PMCs cultured in the presence of LPS showed decreased haptotactic activity to MCP-1. Blocking the CCR2 with neutralizing antibodies decreased the haptotactic response of PMCs to MCP-1. These results suggest that 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 thus contribute to the regeneration of the mesothelium during the process of pleural repair.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Veterans Affairs Medical Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: N
authors.initials: N
authors.lastname: Nasreen
authors.forename: K A
authors.initials: KA
authors.lastname: Mohammed
authors.forename: G
authors.initials: G
authors.lastname: Galffy
authors.forename: M J
authors.initials: MJ
authors.lastname: Ward
authors.forename: V B
authors.initials: VB
authors.lastname: Antony
mesh_terms: D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D010994:Pleura / Q000293:injuries* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
chemical_list: C515334:CCR2 protein, human; D018932:Chemokine CCL2; D007376:Interleukin-2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine