蛋白二硫键异构酶PDI调控组织因子介导的凝血酶生成

Protein disulfide isomerase (PDI) could change the conformation and activity of its substrate by change the disulfide on it. The recent researchs suggested that PDI plays an important role in arterial thrombosis, but of which mechanism is still unknown. In this study, using thrombin generation assay (TGA), we explored the regulation of PDI on tissue factor (TF) mediating thrombin generation. After incubated with inhibitory anti-TF antibody 4501, recombinant PDI protein separately, lipopolysaccharide (LPS)-stimulated human monocyte which expressing TF were incubated with human plasma and fluorescent thrombin substrate. The coagulation was started by addition Ca2+, then thrombin generation was measured. Marrow mononuclear cells isolated from PDI knockout and control mice were stimulated by LPS, which was followed by addition of mouse plasma and fluorescent thrombin substrate and Ca2+, then thrombin generation was measured. Inhibitory anti-TF antibody 4501 could almost completely inhibit the thrombin generation, which suggesting that the coagulation was TF-dependent. PDI deficient marrow mononuclear cells show impaired thrombin generation. PDI up-regulated TF-initiated thrombin generation.