Bacterial induction of pleural mesothelial monolayer barrier dysfunction.
Pneumonia remains one of the most common infectious causes of mortality. Patients with pneumonia develop parapneumonic effusions with a high neutrophil count as well as high protein concentrations. We hypothesized that pulmonary parenchymal bacterial infection causes a permeability change in the pleural 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 heart failure and a 4-fold higher level than pleural fluids secondary to uncomplicated parapneumonic effusions. We also analyzed the influence of live Staphylococcus aureus on mesothelial barrier function using a model of confluent mesothelial monolayers. There was a significant drop in electrical resistance across S. aureus-infected pleural mesothelial cell (PMC) monolayers. Recombinant VEGF also decreases PMC electrical resistance. Neutralizing antibodies to VEGF significantly inhibited the drop in PMC electrical resistance caused by S. aureus. S. aureus infection also caused a significant increase in protein leak across confluent mesothelial monolayers. Our results suggest that bacterial pathogens induce VEGF release in mesothelial cells and alter mesothelial permeability, leading to protein exudation in empyema.
Mohammed
K A
KA
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Veterans Affairs Medical Center, and Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Nasreen
N
N
Hardwick
J
J
Logie
C S
CS
Patterson
C E
CE
Antony
V B
VB
D017097:Electric Impedance; D016724:Empyema, Pleural / Q000150:complications; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D006333:Heart Failure / Q000150:complications; D006801:Humans; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D010539:Permeability; D010994:Pleura / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010996:Pleural Effusion / Q000209:etiology / Q000378:metabolism; D011014:Pneumonia / Q000150:complications; D012333:RNA, Messenger / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000503:physiopathology; D013211:Staphylococcus aureus; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors