Effects of alpha 1-acid glycoprotein on tissue factor expression and tumor necrosis factor secretion in human...

Activated monocytes express tissue factor (TF) and secrete tumor necrosis factor alpha (TNF alpha), which are important in the initiation of blood coagulation and inflammation. We investigated the effect of alpha 1-acid glycoprotein (alpha 1-AGP), an acute phase protein, on the induction of the expression of TF and the secretion of TNF alpha in human monocytes in vitro. The TF activity of both fresh human monocytes and human monocytic cell line U937 significantly increased in a dose-dependent manner after a 6 h incubation with human or bovine alpha 1-AGP. The activity of TF gradually tailed off after 24 h. RT-PCR and Southern blot analysis revealed that TF mRNA synthesis was induced in monocytes. Inhibition of alpha 1-AGP induced TF expression by actinomycin D (ActD) further support that de novo TF mRNA synthesis was required. The specificity of the alpha 1-AGP-induced TF activity was demonstrated by anti-alpha 1-AGP antibody inhibition. TNF alpha secretion in alpha 1-AGP stimulated monocytes was also increased; this could be blocked by pentoxifylline (PTX). The possible contamination of lipopolysaccharide (LPS) in the alpha 1-AGP was excluded by limulus amoebocyte lysate. Therefore, these results indicate that alpha 1-AGP may contribute to the cellular initiation of coagulation and inflammation by increasing TF expression and TNF alpha secretion of monocytes.