Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-3-4
pubmed:abstractText
We have previously described a model of acute lung injury in the mouse in which intravenous administration of lipopolysaccharide (LPS) results in a marked sequestration of neutrophils in the pulmonary microvasculature, although this by itself was not sufficient to induce injury. If the sequestered neutrophils were exposed to zymosan, then a striking increase in pulmonary vascular permeability to albumin was found, suggesting that sequestered neutrophils may produce one or more mediators capable of acting directly on the capillary endothelium. Because activated neutrophils are known to release platelet-activating factor (PAF), we hypothesized that PAF produced locally within the pulmonary capillaries may be the mediator involved. Treatment of mice with the PAF antagonist UK-74,505 prior to administration of zymosan alone or combined LPS and zymosan resulted in a substantial attenuation of lung injury, as measured by the accumulation of extravascular 125I-labeled human serum albumin. UK-74,505 had no effect on neutrophil sequestration as measured by myeloperoxidase activity in whole lung tissue and as assessed by light microscopy. Administration of UK-74,505 after LPS, but before zymosan, was also effective at inhibiting lung injury but again, neutrophil sequestration was unaffected. In contrast, UK-74,505 had no effect on cobra venom factor-induced lung injury and neutrophil sequestration. These data suggest that PAF production is involved in the increases in pulmonary vascular permeability, but not in the sequestration of neutrophils, induced by zymosan alone or by combined LPS and zymosan treatment. Early treatment with PAF antagonists may be beneficial in preventing the development of acute lung injury in humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cobra Venoms, http://linkedlifedata.com/resource/pubmed/chemical/Dihydropyridines, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Peroxidase, http://linkedlifedata.com/resource/pubmed/chemical/Platelet Activating Factor, http://linkedlifedata.com/resource/pubmed/chemical/Platelet Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled, http://linkedlifedata.com/resource/pubmed/chemical/Serum Albumin, http://linkedlifedata.com/resource/pubmed/chemical/Zymosan, http://linkedlifedata.com/resource/pubmed/chemical/cobra venom factor, http://linkedlifedata.com/resource/pubmed/chemical/modipafant, http://linkedlifedata.com/resource/pubmed/chemical/platelet activating factor receptor
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
197-204
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9476906-Animals, pubmed-meshheading:9476906-Capillary Permeability, pubmed-meshheading:9476906-Cobra Venoms, pubmed-meshheading:9476906-Dihydropyridines, pubmed-meshheading:9476906-Disease Models, Animal, pubmed-meshheading:9476906-Extravascular Lung Water, pubmed-meshheading:9476906-Female, pubmed-meshheading:9476906-Humans, pubmed-meshheading:9476906-Imidazoles, pubmed-meshheading:9476906-Lipopolysaccharides, pubmed-meshheading:9476906-Lung, pubmed-meshheading:9476906-Mice, pubmed-meshheading:9476906-Mice, Inbred BALB C, pubmed-meshheading:9476906-Neutrophils, pubmed-meshheading:9476906-Peroxidase, pubmed-meshheading:9476906-Platelet Activating Factor, pubmed-meshheading:9476906-Platelet Membrane Glycoproteins, pubmed-meshheading:9476906-Receptors, Cell Surface, pubmed-meshheading:9476906-Receptors, G-Protein-Coupled, pubmed-meshheading:9476906-Respiratory Distress Syndrome, Adult, pubmed-meshheading:9476906-Serum Albumin, pubmed-meshheading:9476906-Skin, pubmed-meshheading:9476906-Zymosan
pubmed:year
1998
pubmed:articleTitle
Platelet-activating factor plays a pivotal role in the induction of experimental lung injury.
pubmed:affiliation
Applied Pharmacology and Lung Pathology, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't