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Tissue factor Deficiency Increases Alveolar Hemorrhage and Death in Influenza A Infected Mice

tetano

Editor, Senior Moderator
J Thromb Haemost. 2016 Mar 7. doi: 10.1111/jth.13307. [Epub ahead of print]
[h=1]Tissue factor Deficiency Increases Alveolar Hemorrhage and Death in Influenza A Infected Mice.[/h] Antoniak S[SUP]1[/SUP], Tatsumi K[SUP]1[/SUP], Hisada Y[SUP]1[/SUP], Milner JJ[SUP]2[/SUP], Neidich SD[SUP]2[/SUP], Shaver CM[SUP]3[/SUP], Pawlinski R[SUP]1[/SUP], Beck MA[SUP]2[/SUP], Bastarache JA[SUP]3[/SUP], Mackman N[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Influenza A virus (IAV) infection is a common respiratory tract infection that causes considerable morbidity and mortality worldwide.
[h=4]OBJECTIVE:[/h] To investigate the effect of a genetic deficiency of tissue factor (TF) in a mouse model of influenza A infection.
[h=4]METHODS:[/h] Wild-type mice, low tissue factor (LTF) mice and mice with the TF gene deleted in different cell types were infected with a mouse-adapted A/Puerto Rico/8/34 H1N1 strain of IAV. TF expression was measured in the lungs, and bronchoalveolar lavage fluid (BALF) was collected to measure extracellular vesicle TF, activation of coagulation, alveolar hemorrhage and inflammation.
[h=4]RESULTS:[/h] IAV infection of wild-type mice increased lung TF expression, activation of coagulation and inflammation in the BALF, but also led to alveolar hemorrhage. LTF mice and mice with a selective deficiency of TF in lung epithelial cells had low basal levels of TF and failed to increase TF expression after infection; these two strains of mice had more alveolar hemorrhage and death compared with controls. In contrast, deletion of TF in either myeloid cells or endothelial cells and hematopoietic cells did not increase alveolar hemorrhage or death after IAV infection. These results indicate that TF expression in the lung, particularly in epithelial cells, is required to maintain alveolar hemostasis after IAV infection.
[h=4]CONCLUSION:[/h] Our study indicates that TF-dependent activation of coagulation is required to limit alveolar hemorrhage and death after influenza A infection. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.


[h=4]KEYWORDS:[/h] hemorrhage; hemostasis; influenzavirus A; pneumonia; tissue factor

PMID: 26947929 [PubMed - as supplied by publisher]
 
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