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

Activated monocytes express tissue factor (TF) and secrete tumor necrosis factor a (TNFα), which are important in the initiation of blood coagulation and inflammation. We investigated the effect of α1-acid glycoprotein (α1-AGP), an acute phase protein, on the induction of the expression of TF and the secretion of TNFα 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 α1-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 α1-AGP induced TF expression by actinomycin D (ActD) further support that de novo TF mRNA synthesis was required. The specificity of the α1-AGP-induced TF activity was demonstrated by anti-α1-AGP antibody inhibition. TNFα secretion in α1-AGP stimulated monocytes was also increased; this could be blocked by pentoxifylline (PTX). The possible contamination of lipopolysaccharide (LPS) in the α1-AGP was excluded by limulus amoebocyte lysate. Therefore, these results indicate that α1-AGP may contribute to the cellular initiation of coagulation and inflammation by increasing TF expression and TNFα secretion of monocytes.