title: C-reactive protein does not directly induce tissue factor in human monocytes.
abstract: OBJECTIVE
  It is generally assumed that C-reactive protein (CRP) induces synthesis of tissue factor (TF) in monocytic cells, thereby potentially initiating intravascular blood coagulation. We aimed to elucidate the mechanism of CRP-induced TF expression in monocytes and monocyte-derived macrophages (MDMs) in vitro.
  
  
  RESULTS
  Monocytes were isolated from the blood of healthy donors and cultured with or without CRP or lipopolysaccharide (LPS) to study the time course of TF antigen and TF mRNA expression. Addition of 100 microg/mL CRP did not result in a significant increase in TF antigen (range: 9 to 163 pg/10(6) cells, n=11) and TF mRNA (relative number of TF transcripts; N(TF)=0.01 to 0.33), when compared with nonstimulated cells (TF antigen 7 to 46 pg/10(6) cells, N(TF)=0.01 to 0.13). Variation of CRP concentration and exposure time did not affect the TF response. Similar results were obtained in monocytes cultured in suspension and in MDMs. In contrast, TF was strongly induced by 10 microg/mL LPS (TF antigen 1125 to 6120 pg/10(6) cells, N(TF)=5.94 to 23.43). Cultured monocytes did express FcRgammaII, a putative CRP receptor, and addition of CRP induced a 7-fold increase in the production of monocyte chemoattractant protein-1 (MCP-1). Interestingly, CRP addition to peripheral blood mononuclear cells (PBMCs) did result in TF expression on monocytic cells.
  
  
  CONCLUSIONS
  The absence of TF induction after incubation of purified monocytes with CRP indicates that CRP is unable to induce TF expression in monocytes and MDMs directly. The presence of CRP-induced TF expression in PBMCs suggests that CRP can induce TF indirectly, probably through cross-talk between cells.
authors.affiliation: Hemostasis and Thrombosis Research Centre, Department of Hematology, Leiden University Medical Centre, Leiden, The Netherlands. epaffen@lumc.nl
authors.forename: Elaine
authors.initials: E
authors.lastname: Paffen
authors.forename: Hans L
authors.initials: HL
authors.lastname: Vos
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Bertina
mesh_terms: D001773:Blood Cells / Q000502:physiology; D002097:C-Reactive Protein / Q000494:pharmacology* / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D003199:Computer Systems; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018932:Chemokine CCL2; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D002097:C-Reactive Protein; D013925:Thromboplastin