Tissue factor expression in vital organs during murine traumatic shock: role of transcription factors AP-1 and NF-kappaB.
BACKGROUND
Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the extrinsic pathway of coagulation that has been shown to have a role in the pathophysiology of sepsis and reperfusion injury. The purpose of this study was to investigate TF expression in vital organs and to determine possible regulatory mechanisms of TF expression in the lung during traumatic shock in rats.


METHODS
Noble-Collip drum trauma was induced in anesthetized Sprague-Dawley rats. Anesthetized rats without trauma served as controls. TF activity was measured in plasma and lung tissue. TF messenger RNA (mRNA) was measured in the lung, liver, and small intestine using ribonuclease protection assays. Electromobility shift assays were used to quantify binding of nuclear extracts from lung to TF-specific consensus domains for transcription factors NF-kappaB and AP-1.


RESULTS
TF activity in plasma increased up to 14-fold and +232% in the lung (P < 0.001 for plasma and lung) 2 h after trauma. TF mRNA level was significantly increased in the lungs (P < 0.01), small intestine (P < 0.01), and liver (P < 0.05) 1 h after trauma compared to sham-operated control rats. TF mRNA expression continued to increase in the lungs and the liver (both, P < 0.001) 2 h after trauma TF sequence-specific complex binding to AP-1 and NF-kappaB domains was enhanced in the lungs of trauma rats (+395%, P < 0.001 and +168%, P < 0.001, respectively).


CONCLUSIONS
These results suggest that TF may play an important role in the pathophysiology of severe trauma and that regulatory elements AP-1 and NF-kappaB may be involved in the regulation of TF mRNA expression in traumatic shock.
Armstead
V E
VE
Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-5507, USA. Valerie.Armstead@mail.tju.edu
Opentanova
I L
IL
Minchenko
A G
AG
Lefer
A M
AM
D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012260:Ribonucleases / Q000378:metabolism; D012774:Shock, Traumatic / Q000378:metabolism* / Q000503:physiopathology; D013925:Thromboplastin / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D013925:Thromboplastin; D012260:Ribonucleases