Low levels of tissue factor lead to alveolar haemorrhage, potentiating murine acute lung injury and oxidative stress.
Thorax
; 67(12): 1032-9, 2012 Dec.
Article
in En
| MEDLINE
| ID: mdl-23033361
ABSTRACT
BACKGROUND:
Systemic blockade of tissue factor (TF) attenuates acute lung injury (ALI) in animal models of sepsis but the effects of global TF deficiency are unknown. We used mice with complete knockout of mouse TF and low levels (â¼1%) of human TF (LTF mice) to test the hypothesis that global TF deficiency attenuates lung inflammation in direct lung injury.METHODS:
LTF mice were treated with 10 µg of lipopolysaccharide (LPS) or vehicle administered by direct intratracheal injection and studied at 24 h.RESULTS:
Contrary to our hypothesis, LTF mice had increased lung inflammation and injury as measured by bronchoalveolar lavage cell count (3.4×10(5) wild-type (WT) LPS vs 3.3×10(5) LTF LPS, p=0.947) and protein (493 µg/ml WT LPS vs 1014 µg/ml LTF LPS, p=0.006), proinflammatory cytokines (TNF-α, IL-10, IL-12, p<0.035 WT LPS vs LTF LPS) and histology compared with WT mice. LTF mice also had increased haemorrhage and free haemoglobin in the airspace accompanied by increased oxidant stress as measured by lipid peroxidation products (F(2) isoprostanes and isofurans).CONCLUSIONS:
These findings indicate that global TF deficiency does not confer protection in a direct lung injury model. Rather, TF deficiency causes increased intra-alveolar haemorrhage following LPS leading to increased lipid peroxidation. Strategies to globally inhibit TF may be deleterious in patients with ALI.
Full text:
1
Database:
MEDLINE
Main subject:
Pulmonary Alveoli
/
Thromboplastin
/
Oxidative Stress
/
Acute Lung Injury
/
Hemorrhage
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Year:
2012
Type:
Article