title: Platelet-derived growth factor-BB and monocyte chemotactic protein-1 induce human peripheral blood monocytes to express tissue factor.
abstract: Monocytes induced to express tissue factor (TF), the initiator of the clotting cascade, might play an important role in the pathogenesis of atherosclerosis. We have investigated the TF-inducing capacity of two factors thought to be involved in atherogenesis, i.e. the platelet derived growth factor-BB (PDGF-BB) and monocyte chemotactic protein-1 (MCP-1), a member of the chemokine superfamily. PDGF-BB and MCP-1 are potent chemotactic and activating factors for human blood monocytes. alpha-thrombin which is known to induce TF in endothelial cells and that recently has been shown to induce secretion of MCP-1 from endothelial cells and monocytes was also studied. PDGF-BB induced a dose-dependent expression of TF-antigen in monocytes with maximal response at 20-50 ng/mL. At higher concentrations the expression was reduced. No synergistic effect between PDGF-BB and LPS was seen. MCP-1 also induced a dose-dependent TF-expression with maximal response at 50 ng/mL. In contrast to these results thrombin did not. MCP-1 had a slight, but not significant, priming effect on LPS-induced TF expression. These data show that PDGF-BB and MCP-1 are potent inducers of TF in human peripheral blood monocytes. We suggest that this TF-induction might be an important link between hemostasis and inflammation.
authors.affiliation: Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ernofsson
authors.forename: A
authors.initials: A
authors.lastname: Siegbahn
mesh_terms: D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology; D000077214:Becaplermin; D018932:Chemokine CCL2 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D013268:Stimulation, Chemical; D013917:Thrombin / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D013925:Thromboplastin; D013917:Thrombin