Platelet-derived growth factor-BB and monocyte chemotactic protein-1 induce human peripheral blood monocytes to express tissue factor.
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.
Ernofsson
M
M
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
Siegbahn
A
A
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
D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D013925:Thromboplastin; D013917:Thrombin