Linked Life Data

19166484

Source:http://linkedlifedata.com/resource/pubmed/id/19166484

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11-12
pubmed:dateCreated
2010-4-16
pubmed:abstractText
Transmigration of neutrophils through the microvascular endothelium is a cardinal event of acute inflammation. It has been suggested that gap junctions made of connexin43 (Cx43) may serve as a conducting pathway to spread inflammatory signals within the lung capillary network. To determine whether Cx43 contributes to neutrophil transmigration in vivo, the number of transmigrated neutrophils was monitored in lungs of Cx43 mouse models subjected to inflammation by intratracheal instillations of Pseudomonas aeruginosa lipopolysaccharide (LPS). Cx43 was detected in inflamed lungs independently of neutrophil recruitment, whereas Cx43 up-regulation was not detected in mice genetically protected from inflammation. Mice heterozygous for the Cx43 gene (gja1) showed a 56% (P < 0.01) reduction in airway neutrophil count. In contrast, increased (P < 0.05) neutrophil recruitment in response to LPS was observed in a mouse model expressing a mutant Cx43 with enhanced channel conductivity. In vitro adhesion assays showed that reduced conductivity of Cx43 channels with (43)Gap26, a Cx43 blocking peptide, decreased adhesion of neutrophils to endothelial cells. Finally, we found that instillation of (43)Gap26 in inflamed lungs reduced neutrophil transmigration by 65% (P < 0.05). These results indicate that inflammatory mediators up-regulate alveolar Cx43 to promote neutrophil recruitment to the airspace. Cx43 may therefore represent a pharmacological target in lung diseases characterized by excessive neutrophil recruitment to the airways.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1582-4934
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4560-70
pubmed:meshHeading
pubmed:articleTitle
Connexin43 modulates neutrophil recruitment to the lung.
pubmed:affiliation
Laboratory of Clinical Investigation III, Department of Pediatrics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't