title: Clinically applicable thermal preconditioning attenuates leukocyte-endothelial interactions.
abstract: BACKGROUND
  We have previously demonstrated that clinically applicable thermal preconditioning induces heat shock protein 72 (HSP72) and protects against a subsequent ischemia-reperfusion (I/R) injury in an animal model. A core component of I/R injuries is the interaction between activated leukocytes and endothelial cells. We hypothesized that the effects of clinically applicable thermal preconditioning are mediated through attenuation of this leukocyte-endothelial (L-E) interaction.
  
  
  METHODS
  Twenty-one male Sprague Dawley rats were divided into control, I/R, and preconditioning plus I/R groups. Preconditioning was done under general anesthesia and the animals' temperature raised by 1 degrees C for 15 minutes in a water bath. This was repeated once a day for 5 successive days. I/R injury was caused by occlusion of the superior mesenteric artery for 10 minutes followed by 1 hour of reperfusion. L-E interactions were analyzed using intravital microscopy of a mesenteric vessel in vivo. L-E interactions were determined using leukocyte velocity (which decreases as cells interact), and number of adherent and migrated leukocytes. HSP72 was assessed by Western blot.
  
  
  RESULTS
  Ischemia-reperfusion caused a decrease in leukocyte rolling velocity at all timepoints (p < 0.05 versus controls). Preconditioning attenuated the effects of I/R, and leukocyte rolling velocity was significantly improved versus I/R (p < 0.05) to levels similar to those in controls. Similarly, the number of adherent and migrating leukocytes increased significantly (p < 0.05) after I/R versus control at all time points, and preconditioning attenuated these to control levels, (p < 0.05 versus I/R) at both the 30- and 60-minute postischemia time points. Upregulation of HSP72 was demonstrated on Western blot.
  
  
  CONCLUSIONS
  These results demonstrate that the benefit of clinically applicable thermal preconditioning is at least partially because of an immunomodulatory role in attenuating leukocyte-endothelial interactions associated with an increased expression of HSP 72.
authors.affiliation: Department of Surgery, Royal College of Surgeons of Ireland, Beaumont Hospital, Dublin, Ireland.
authors.forename: Paul H
authors.initials: PH
authors.lastname: McCormick
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Sean
authors.initials: S
authors.lastname: Tierney
authors.forename: Cathal J
authors.initials: CJ
authors.lastname: Kelly
authors.forename: David J
authors.initials: DJ
authors.lastname: Bouchier-Hayes
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001783:Blood Flow Velocity; D015153:Blotting, Western; D001831:Body Temperature; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis; D006358:Hot Temperature; D019194:Ischemic Preconditioning; D007962:Leukocytes / Q000166:cytology*; D008297:Male; D008643:Mesentery / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins