title: Ionizing radiation induces upregulation of cellular procoagulability and tissue factor expression in human peripheral blood mononuclear cells.
abstract: BACKGROUND
  The therapeutic application of ionizing radiation is associated with thrombotic events, but the exact underlying molecular mechanisms are still unclear. Tissue factor (TF), the primary initiator of blood coagulation, is essentially involved in the pathophysiology of thrombosis. Circulating monocytes have been identified to upregulate TF under inflammatory conditions and, thereby, enhance blood thrombogenicity. The study examines the effect of irradiation on the cellular procoagulability and TF protein expression of human peripheral blood mononuclear cells (PBMNCs) in a time period of 7 days.
  
  
  METHODS
  Human PBMNCs were irradiated with 20 Gy. Procoagulability of PBMNCs, released microparticles and microparticle-free cell supernatant was analyzed by a chromogenic assay and TF protein expression quantified by TF ELISA. To determine whether irradiated PBMNCs and shed microparticles initiate plasma clotting, a one stage clotting assay was performed.
  
  
  RESULTS
  We found a significant increase of PBMNC-associated procoagulant activity over a time period of 7 days post irradiation. Moreover, 3 days post irradiation PBMNCs initiated the plasma clotting faster than non-irradiated cells. An enhanced cellular TF protein concentration was persistently observed throughout the investigated time up to 7 days post irradiation. Microparticle-associated TF activity significantly increased 3 days post irradiation compared with the non-irradiated controls. PBMNC-derived microparticles post irradiation also initiated the plasma clotting faster than microparticles derived from controls.
  
  
  CONCLUSIONS
  The results show irradiation to induce TF expression and to increase procoagulability of PBMNCs and cell-derived microparticles. This could be a possible mechanism by which ionizing radiation enhances blood thrombogenicity.
authors.affiliation: Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Goldin-Lang
authors.forename: Florian
authors.initials: F
authors.lastname: Niebergall
authors.forename: Silvio
authors.initials: S
authors.lastname: Antoniak
authors.forename: Bjoern
authors.initials: B
authors.lastname: Szotowski
authors.forename: Peter
authors.initials: P
authors.lastname: Rosenthal
authors.forename: Klaus
authors.initials: K
authors.lastname: Pels
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
mesh_terms: D001777:Blood Coagulation / Q000276:immunology* / Q000528:radiation effects*; D002478:Cells, Cultured; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D010316:Particle Size; D011839:Radiation, Ionizing; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology / Q000276:immunology; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology / Q000528:radiation effects
chemical_list: D013925:Thromboplastin