Bacterial induction of pleural mesothelial monolayer barrier dysfunction

Pneumonia remains one of the most common infectious causes of mortality. Pa tients with pneumonia develop parapneumonic effusions with a high neutrophi l count as well as high protein concentrations. We hypothesized that pulmon ary parenchymal bacterial infection causes a permeability change in the ple ural mesothelium by inducing the production of vascular endothelial growth factor (VEGF). Complicated parapneumonic pleural effusions (empyema) have a 19-fold higher VEGF level than pleural fluids secondary to congestive hear t failure and a 4-fold higher level than pleural fluids secondary to uncomp licated parapneumonic effusions. We also analyzed the influence of live Sta phylococcus aureus on mesothelial barrier function using a model of conflue nt mesothelial monolayers. There was a significant drop in Electrical resis tance across S. aureus-infected pleural mesothelial cell (PMC) monolayers. Recombinant VEGF also decreases PMC electrical resistance. Neutralizing ant ibodies to VEGF significantly inhibited the drop in PMC electrical resistan ce caused by S. aureus. S. aureus infection also caused a significant incre ase in protein leak across confluent mesothelial monolayers. Our results su ggest that bacterial pathogens induce VEGF release in mesothelial cells and alter mesothelial permeability, leading to protein exudation in empyema.