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

Tissue factor (TF) is the primary cellular initiator of the coagulation pro tease cascade and serves as a cell surface receptor and a specific cofactor for plasma factors VII/VIIa. Because there is evidence that TF is regulate d by a P-selectin dependent gene, we examined TF mRNA expression in the lun gs 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 th at 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 exh ibited reduced TF mRNA expression (-34%; P < 0.001) after systemic administ ration of rsPSGL.Ig. The expression of TF mRNA was also significantly decre ased (-29%, P < 0.05) in the lungs of P-selectin -/- mice compared with wil d-type control C57B16 mice. The present results provide evidence for a P-se lectin-dependent mechanism that enhances TF gene expression in traumatic sh ock. The major support for this mechanism is that either blockade of P-sele ctin by rsPSGL.Ig or deletion of the P-selectin gene leads to significant d ecreases in TF mRNA expression in the lung. These results are consistent wi th the concept that TF interacting with P-selectin may play a significant r ole in the pathophysiology of trauma.