Mycobacteria Induces Pleural Mesothelial Permeability by Down-Regulating [beta]-Catenin Expression

Byline: K. A. Mohammed (1), N. Nasreen (1), J. Hardwick (1), R. D. Horn (1), K. L. Sanders (1), V. B. Antony (1) Keywords: Vascular endothelial growth factor; Mesothelial cells; Mycobacterium; N-cadherin; [beta]-catenin; Protein permeability Abstract: Patients with pulmonary tuberculosis develop pleural effusions with a high protein content. Pleural mesothelial adherens junctions promote mesothelial cell-cell adhesion and contribute to pleural integrity. In the present study we have investigated the effect of mycobacterium (BCG) on mesothelial cell adherens junction proteins and pleural permeability. BCG enhanced pleural mesothelial cell (PMC) release of vascular endothelial growth factor (VEGF), and decreased electrical resistance across the PMC monolayer. Neutralizing antibodies to VEGF significantly restored the drop in PMC electrical resistance caused by BCG. BCG infection down regulated [beta]-catenin (adherens junction protein) expression and caused increased permeability across confluent mesothelial monolayer. Our results suggest that in TB pleurisy, mycobacteria cause VEGF release from mesothelial cells and leads to protein exudation by altering mesothelial adherens junction proteins. Author Affiliation: (1) Division of Pulmonary and Critical Care Medicine, Department of Medicine, Veterans' Affairs Medical Center, Indiana University School of Medicine, 1481 West 10th Street, 111-P, Indianapolis, IN 46202, USA Article History: Accepted Date: 10/02/2003