Pulmonary tissue factor mRNA expression during murine traumatic shock: effect of P-selectin blockade

• Published in: Shock (Augusta, Ga.) Vol. 15; no. 4; p. 323
• Main Authors: Armstead, V E, Minchenko, A G, Scalla, R, Lefer, A M
• Format: Journal Article
• Language: English
• Published: United States 01.04.2001
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Gene Expression Regulation - drug effects; Immunoconjugates - pharmacology; Immunoconjugates - therapeutic use; Lung - drug effects; Lung - metabolism; Male; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - pharmacology; Membrane Glycoproteins - physiology; Membrane Glycoproteins - therapeutic use; Mice; Mice, Knockout; P-Selectin - genetics; P-Selectin - physiology; Rats; Rats, Sprague-Dawley; RNA, Messenger - biosynthesis; Shock, Traumatic - genetics; Shock, Traumatic - metabolism; Thromboplastin - biosynthesis; Thromboplastin - genetics; Thromboplastin - physiology
• ISSN: 1073-2322
• DOI: 10.1097/00024382-200115040-00013

Tissue factor (TF) is the primary cellular initiator of the coagulation protease cascade and serves as a cell surface receptor and a specific cofactor for plasma factors VII/VIIa. Because there is evidence that TF is regulated by a P-selectin dependent gene, we examined TF mRNA expression in the lungs during murine traumatic shock in the presence and absence of recombinant soluble P-selectin glycoprotein ligand-1 (rsPSGL.Ig) by using ribonuclease protection assays. Moreover, we studied the level of TF mRNA expression in mice with their P-selectin gene deleted (P-selectin -/-). Our data show that TF mRNA was significantly increased (+143%; P < 0.001) in the lungs 2 h after trauma compared with control rats subjected to sham trauma, which exhibited reduced TF mRNA expression (-34%; P < 0.001) after systemic administration of rsPSGL.Ig. The expression of TF mRNA was also significantly decreased (-29%; P < 0.05) in the lungs of P-selectin -/- mice compared with wild-type control C57B16 mice. The present results provide evidence for a P-selectin-dependent mechanism that enhances TF gene expression in traumatic shock. The major support for this mechanism is that either blockade of P-selectin by rsPSGL.Ig or deletion of the P-selectin gene leads to significant decreases in TF mRNA expression in the lung. These results are consistent with the concept that TF interacting with P-selectin may play a significant role in the pathophysiology of trauma.