The role of PSGL-1 in pathogenesis of systemic inflammatory response and coagulopathy in endotoxemic mice.

INTRODUCTION

Endotoxemia often results in systemic inflammatory response syndrome (SIRS), coagulation disturbance and acute lung injury (ALI), and such a condition is associated with the activation of platelets, leukocytes and vascular endothelial cells (VECs). P-selectin glycoprotein ligand 1 (PSGL-1) is a key regulatory molecule in the activation of platelets, leukocytes and VECs. However, it still remains largely unexplored whether PSGL-1 plays an important role in SIRS, coagulation dysfunction and ALI of endotoxemia. In the present study, we aimed to study the role of PSGL-1 in above-mentioned situations using endotoxemic mice.

MATERIALS AND METHODS

An endotoxemia model was established in BALB/c mice via lipopolysaccharide (LPS) administration. Moreover, the mice were simultaneously injected with PSGL-1 antibody for intervention. The survival rate, morphologic changes of lung tissues, platelet-leukocyte adhesion, tissue factor expression on leukocytes, fibrinogen deposition in lung tissues, serum levels of inflammatory factors and the activation of VECs were determined.

RESULTS

The results showed that the aggregation and recruitment of platelets and leukocytes in lung tissues, the expression of tissue factor on leukocytes, the serum levels of inflammatory factors, the activation of VECs, and the fibrinogen deposition in lung tissues were increased in endotoxemic mice, which were significantly alleviated by administration of PSGL-1 antibody. Moreover, blockade of PSGL-1 markedly increased survival rate, and alleviated coagulation disturbance and lung injury in endotoxemic mice.

CONCLUSIONS

Taken together, PSGL-1 played an important role in pathogenesis of SIRS and coagulation dysfunction and ALI in endotoxemic mice.