RGD Reference Report - Plasminogen activator inhibitor type 1 is protective during severe Gram-negative pneumonia. - Rat Genome Database

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Plasminogen activator inhibitor type 1 is protective during severe Gram-negative pneumonia.

Authors: Renckens, R  Roelofs, JJ  Bonta, PI  Florquin, S  De Vries, CJ  Levi, M  Carmeliet, P  Van't Veer, C  Van der Poll, T 
Citation: Renckens R, etal., Blood. 2007 Feb 15;109(4):1593-601. Epub 2006 Oct 10.
RGD ID: 4144840
Pubmed: PMID:17032919   (View Abstract at PubMed)
DOI: DOI:10.1182/blood-2006-05-025197   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SERPINE1Humanbacterial pneumonia severityISOSerpine1 (Mus musculus) RGD 
Serpine1Ratbacterial pneumonia severityISOSerpine1 (Mus musculus) RGD 
Serpine1Mousebacterial pneumonia severityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpine1  (serpin family E member 1)

Genes (Mus musculus)
Serpine1  (serine (or cysteine) peptidase inhibitor, clade E, member 1)

Genes (Homo sapiens)
SERPINE1  (serpin family E member 1)


Additional Information