RGD Reference Report - Crosstalk between thrombosis and inflammation in lung reperfusion injury. - Rat Genome Database

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Crosstalk between thrombosis and inflammation in lung reperfusion injury.

Authors: Farivar, AS  Delgado, MF  McCourtie, AS  Barnes, AD  Verrier, ED  Mulligan, MS 
Citation: Farivar AS, etal., Ann Thorac Surg. 2006 Mar;81(3):1061-7.
RGD ID: 5131904
Pubmed: PMID:16488723   (View Abstract at PubMed)
DOI: DOI:10.1016/j.athoracsur.2005.09.047   (Journal Full-text)

BACKGROUND: Activation of extravascular coagulation has been reported in acute lung injury models of sepsis and acute respiratory distress syndrome. Thrombin, the main effector protease of extravascular coagulation, activates proinflammatory cell types, including macrophages, endothelial cells, and neutrophils, each of which participates in lung ischemia-reperfusion injury. We used hirudin, a potent, specific direct thrombin inhibitor, to define the role of thrombin in lung ischemia-reperfusion injury. METHODS: Rats were pretreated with hirudin 30 minutes before warm, in situ left lung ischemia and reperfusion. Multiple in vivo assessments of lung injury were determined, and mechanistic studies assessed transcriptional regulation early in reperfusion and proinflammatory protein secretion late in reperfusion. Immunohistochemistry localized thrombin activation. RESULTS: Thrombin localized to macrophages and endothelial and epithelial cells early in reperfusion. Hirudin significantly limited lung ischemia-reperfusion injury-induced derangements in vascular permeability and intraalveolar inflammatory cell sequestration, resulting in improved arterial oxygenation after ischemia and 4 hours of reperfusion. The protection was transcriptionally mediated by attenuated activator protein-1 and early growth response-1 transactivation, but not nuclear factor kappa B transactivation. This was associated with reduced chemokine, but not tumor necrosis factor alpha, secretion late in reperfusion. CONCLUSIONS: Thrombin promotes lung ischemia-reperfusion injury, as hirudin protected against experimental acute lung injury. Hirudin conferred protection through a mechanism independent of nuclear factor kappa B and tumor necrosis factor alpha, suggesting that its effects may be mediated by a parallel, synergistic inflammatory pathway through activator protein-1 and early growth response-1.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Reperfusion Injury  ISOEgr1 (Rattus norvegicus)5131904; 5131904Lung Reperfusion Injury more ...RGD 
Reperfusion Injury  IEP 5131904Lung Reperfusion Injury more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egr1  (early growth response 1)

Genes (Mus musculus)
Egr1  (early growth response 1)

Genes (Homo sapiens)
EGR1  (early growth response 1)


Additional Information