title: Role of MCP-1 in pleural effusion development in a carrageenan-induced murine model of pleurisy.
abstract: Exudative pleural effusions affect over 1500 patients per million population each year. The pathobiology of pleural exudate formation remains unclear. Our recent study revealed monocyte chemotactic protein-1 (MCP-1) as a key driver of fibrinolytic-induced exudate effusion while another study found a role for MCP-1 in malignant effusion formation. In the present study, we further evaluated the role of MCP-1 in the development of pleural effusion in a mouse model of acute pleural inflammation.
  
  
  
  λ-Carrageenan (CAR) was injected into the pleural cavity of CD1 mice and pleural effusion volume measured up to 16 h post-injection. Pleural effusion and serum protein and MCP-1 concentrations were measured and differential cell counts performed in fluids. Mice were also treated with either intraperitoneal (i) anti-MCP-1 antibody or isotype control or (ii) an MCP-1 receptor (CCR2) antagonist or vehicle control 12 h prior to and at the time of CAR injection.
  
  
  
  Intrapleural CAR induced significant pleural fluid accumulation (300.0 ± 49.9 μL) in mice after 4 h. Pleural fluid MCP-1 concentrations were significantly higher than corresponding serum MCP-1 (144 603 ± 23 204 pg/mL vs 3703 ± 801 pg/mL, P < 0.0001). A significant decrease in pleural fluid formation was seen both with anti-MCP-1 antibody (median (interquartile range, IQR): 36 (0-168) μL vs controls 290 (70-436) μL; P = 0.02) or CCR2 antagonist (153 (30-222) μL vs controls 240 (151-331) μL, P = 0.0049).
  
  
  
  Blockade of MCP-1 activity significantly reduced inflammatory pleural effusion formation in a CAR model. Together with recent successes in MCP-1 blockade in other effusion formation models, our data strongly support clinical evaluation of MCP-1 antagonists as a novel approach to pleural fluid management.
authors.affiliation: Centre for Respiratory Health, School of Medicine & Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Lansley
authors.affiliation: Centre for Respiratory Health, School of Medicine & Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Hui Min
authors.initials: HM
authors.lastname: Cheah
authors.affiliation: Centre for Respiratory Health, School of Medicine & Pharmacology, University of Western Australia, Perth, Western Australia, Australia.|Respiratory Department, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
authors.forename: Y C Gary
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation; D051379:Mice; D010994:Pleura / Q000473:pathology; D010996:Pleural Effusion / Q000378:metabolism*; D010998:Pleurisy / Q000378:metabolism*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D002351:Carrageenan
keywords: carrageenan; monocyte chemotactic protein-1; pleural effusion; pleural inflammation