| First Author | Renckens R | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 4 | Pages | 1593-601 |
| PubMed ID | 17032919 | Mgi Jnum | J:144462 |
| Mgi Id | MGI:3830955 | Doi | 10.1182/blood-2006-05-025197 |
| Citation | Renckens R, et al. (2007) Plasminogen activator inhibitor type 1 is protective during severe Gram-negative pneumonia. Blood 109(4):1593-601 |
| abstractText | Plasminogen activator inhibitor type-1 (PAI-1) levels are consistently elevated in patients with severe pneumonia and sepsis and highly predictive for an unfavorable outcome. In addition, pneumonia is associated with strongly elevated PAI-1 levels in the pulmonary compartment. However, whether PAI-1 causally affects antibacterial host defense in vivo remains unknown. We report here that pneumonia caused by the common respiratory pathogen Klebsiella pneumoniae is associated with local production of PAI-1 in the lungs of wild-type mice. PAI-1 deficiency impaired host defense as reflected by enhanced lethality and increased bacterial growth and dissemination in mice with a targeted deletion of the PAI-1 gene. Conversely, transgenic overexpression of PAI-1 in the lung using a replication-defective adenoviral vector markedly improved host defense against Klebsiella pneumonia and sepsis. PAI-1 deficiency reduced accumulation of neutrophils in the lungs during pneumonia, whereas PAI-1 overexpression in healthy lungs resulted in neutrophil influx, suggesting that PAI-1 protects the host against Klebsiella pneumonia by promoting neutrophil recruitment to the pulmonary compartment. These data demonstrate for the first time that PAI-1 is essential for host defense against severe Gram-negative pneumonia. |
