title: Cold induces reactive oxygen species production and activation of the NF-kappa B response in endothelial cells and inflammation in vivo.
abstract: BACKGROUND
  Organs intended for transplantation are generally stored in the cold for better preservation of their function. However, following transplantation and reperfusion, the microvasculature of transplanted organs often proves to be activated. Extensive leukocyte adhesion and microthrombus formation contribute to failure of the transplanted organ.
  
  
  OBJECTIVE
  In this study we analyzed cold-induced changes to the activation status of cultured endothelial cells, possibly contributing to organ failure.
  
  
  METHODS
  We exposed human umbilical vein endothelial cells (HUVECs) to temperatures below 37 °C (mostly to 8 °C) for 30 min and upon rewarming to 37 °C kept incubating them for up to 24 h. We also in vivo locally exposed mice to cold.
  
  
  RESULTS
  The exposure to low temperatures induced, in HUVECs, expression of the prothrombotic factors plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) and of the inflammatory adhesion molecules, E-selectin, intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, upon rewarming for 30 min, we detected activation of the inflammatory NF-κB pathway, as measured by transient NF-κB translocation to the nucleus and IκBα degradation. Using butylated hydroxytoluene (BHT), a scavenger of reactive oxygen species (ROS), we further demonstrated that cold-induced NF-κB activation depends on ROS production. Local exposure to cold also, in vivo, induced ROS production and ICAM-1 expression and resulted in leukocyte infiltration.
  
  
  CONCLUSIONS
  Our results point to a causative link between ROS production and NF-κB activation, suppression of which had been shown to be beneficial during hypothermic storage and subsequent rewarming of organs for transplantation.
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: E M
authors.initials: EM
authors.lastname: Awad
authors.forename: S Y
authors.initials: SY
authors.lastname: Khan
authors.forename: B
authors.initials: B
authors.lastname: Sokolikova
authors.forename: P M
authors.initials: PM
authors.lastname: Brunner
authors.forename: D
authors.initials: D
authors.lastname: Olcaydu
authors.forename: J
authors.initials: J
authors.lastname: Wojta
authors.forename: J M
authors.initials: JM
authors.lastname: Breuss
authors.forename: P
authors.initials: P
authors.lastname: Uhrin
mesh_terms: D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003080:Cold Temperature; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015815:Cell Adhesion Molecules; D017931:DNA Primers; D016328:NF-kappa B; D017382:Reactive Oxygen Species
keywords: NF-kappa B; cold temperature; endothelial cells; organ transplantation; reactive oxygen species