Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2003-5-21
pubmed:abstractText
Urokinase plasminogen activator (uPA) is a serine protease that catalyzes the conversion of plasminogen to plasmin. Although increased circulating levels of uPA are present in endotoxemia and sepsis, conditions in which activated neutrophils contribute to the development of acute organ dysfunction, the ability of uPA to participate directly in LPS-induced neutrophil activation has not been examined. In the present experiments, we show that uPA can enhance activation of neutrophils exposed to submaximal stimulatory doses of LPS. In particular, uPA increased LPS-induced activation of intracellular signaling pathways, including Akt and c-Jun N-terminal kinase, nuclear translocation of the transcriptional regulatory factor NF-kappa B, and expression of proinflammatory cytokines, including IL-1 beta, macrophage-inflammatory protein-2, and TNF-alpha. There was no effect of uPA on LPS-induced activation of p38 mitogen-activated protein kinase in neutrophils. Transgenic mice unable to produce uPA (uPA(-/-)) were protected from endotoxemia-induced lung injury, as determined by development of lung edema, pulmonary neutrophil accumulation, lung IL-1 beta, macrophage-inflammatory protein-2, and TNF-alpha cytokine levels. These results demonstrate that uPA can potentiate LPS-induced neutrophil responses and also suggest that such effects are sufficiently important in vivo to play a major contributory role in neutrophil-mediated inflammatory responses, such as the development of acute lung injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5644-51
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12759445-Active Transport, Cell Nucleus, pubmed-meshheading:12759445-Acute Disease, pubmed-meshheading:12759445-Animals, pubmed-meshheading:12759445-Cytokines, pubmed-meshheading:12759445-Drug Synergism, pubmed-meshheading:12759445-Enzyme Activation, pubmed-meshheading:12759445-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:12759445-Lipopolysaccharides, pubmed-meshheading:12759445-Lung, pubmed-meshheading:12759445-Male, pubmed-meshheading:12759445-Mice, pubmed-meshheading:12759445-Mice, Inbred BALB C, pubmed-meshheading:12759445-Mice, Inbred C57BL, pubmed-meshheading:12759445-Mice, Knockout, pubmed-meshheading:12759445-Mice, Transgenic, pubmed-meshheading:12759445-Mitogen-Activated Protein Kinases, pubmed-meshheading:12759445-NF-kappa B, pubmed-meshheading:12759445-Neutrophil Activation, pubmed-meshheading:12759445-Neutrophils, pubmed-meshheading:12759445-Protein-Serine-Threonine Kinases, pubmed-meshheading:12759445-Proto-Oncogene Proteins, pubmed-meshheading:12759445-Proto-Oncogene Proteins c-akt, pubmed-meshheading:12759445-Up-Regulation, pubmed-meshheading:12759445-Urokinase-Type Plasminogen Activator, pubmed-meshheading:12759445-p38 Mitogen-Activated Protein Kinases
pubmed:year
2003
pubmed:articleTitle
Urokinase-type plasminogen activator potentiates lipopolysaccharide-induced neutrophil activation.
pubmed:affiliation
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. edward.abraham@uchsc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.