C5A INDUCES TISSUE FACTOR ACTIVITY ON ENDOTHELIAL-CELLS

Tissue factor (TF) is an integral membrane glycoprotein that serves as a cofactor for blood coagulation factor VIIa. The induction of TF on the surface of endothelial cells is initiated by various stimuli inclu ding lipopolysaccharide, interleukin-1 beta, and tumor necrosis factor alpha. We have demonstrated that recombinant human C5a induces TF act ivity in a dose-dependent fashion in human umbilical vein endothelial cells (HUVEC). Peak activity (4.9-fold increase) was obtained 3-6 h af ter treatment with 10 mu M C5a. TF mRNA as assessed by RT-PCR method w as also significantly increased (3.75-fold) after 3 h incubation with C5a, suggesting that C5a induces TF activity on HUVEC, at least in par t, by enhancing the level of TF mRNA. The increase in TF activity by C 5a was inhibited by methylprednisolone. The induction of TF on endothe lial cells by C5a may represent one of many potential interrelationshi ps between the inflammatory and coagulation schemes.