RGD Reference Report - Priming for enhanced alveolar fibrin deposition after hemorrhagic shock: role of tumor necrosis factor. - Rat Genome Database

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Priming for enhanced alveolar fibrin deposition after hemorrhagic shock: role of tumor necrosis factor.

Authors: Fan, J  Kapus, A  Li, YH  Rizoli, S  Marshall, JC  Rotstein, OD 
Citation: Fan J, etal., Am J Respir Cell Mol Biol. 2000 Apr;22(4):412-21.
RGD ID: 11080967
Pubmed: PMID:10745022   (View Abstract at PubMed)
DOI: DOI:10.1165/ajrcmb.22.4.3857   (Journal Full-text)

Hemorrhagic shock due to major trauma predisposes to the development of acute respiratory distress syndrome. Because lung fibrin deposition is one of the hallmarks of this syndrome, we hypothesized that resuscitated shock might predispose to the development of a net procoagulant state in the lung. A rodent model of shock/resuscitation followed by low-dose intratracheal lipopolysaccharide (LPS), a clinically relevant "two-hit" model, was used to test this hypothesis. Resuscitated shock primed the lungs for an increased tissue factor and plasminogen activator (PA) inhibitor-1 gene expression in response to LPS, while the fibrinolytic PA was reduced. These alterations were recapitulated in isolated alveolar macrophages, suggesting their role in the process. LPS-induced tumor necrosis factor (TNF) was also augmented in animals after antecedent shock/resuscitation, and studies using anti-TNF antibodies revealed that TNF expression was critical to the induction of the procoagulant molecules and the reduction in PA. By contrast, TNF did not appear to play an important role in neutrophil sequestration in this model, inasmuch as anti-TNF had no effect on lung neutrophil accumulation or chemokine expression. However, treatment prevented albumin leak by preventing alveolar neutrophil activation. The inclusion of the antioxidant N-acetyl-cysteine in the resuscitation fluid resulted in prevention of both the development of the net procoagulant state and lung neutrophil sequestration, suggesting a role for upstream oxidant effects in the priming process. These studies provide a cellular and molecular basis for lung fibrin deposition after resuscitated shock and demonstrate a divergence of pathways responsible for fibrin generation and neutrophil accumulation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SERPINE1HumanAcute Lung Injury  ISOSerpine1 (Rattus norvegicus)associated with Shock more ...RGD 
Serpine1RatAcute Lung Injury  IEP associated with Shock more ...RGD 
Serpine1MouseAcute Lung Injury  ISOSerpine1 (Rattus norvegicus)associated with Shock more ...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