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Role of MCP ‐1 in pleural effusion development in a carrageenan‐induced murine model of pleurisy
Author(s) -
Lansley Sally M.,
Cheah Hui Min,
Lee Y.C. Gary
Publication year - 2017
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.12951
Subject(s) - medicine , pleurisy , pleural effusion , effusion , immunology , cancer research , pathology , surgery
Background and objective 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. Methods 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. Results 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). Conclusions 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.