title: Radiation-induced platelet-endothelial cell interactions are mediated by P-selectin and P-selectin glycoprotein ligand-1 in the colonic microcirculation.
abstract: BACKGROUND
  Antiplatelet reagents have been reported to protect against intestinal damage associated with abdominal radiotherapy, but the mechanisms behind radiation-induced platelet-endothelium interactions are not known. We sought to define the adhesive mechanisms that regulate radiotherapy-induced platelet-endothelial cell interactions in the colon.
  
  
  METHODS
  All mice except the controls were exposed to abdominal radiation with a single dose of 20 Gray. Mice were pretreated with an isotype-matched control antibody or a monoclonal antibody directed against either P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1). Platelet and leukocyte rolling and adhesion in the colon were determined by use of inverted intravital fluorescence microscopy 16 hours after radiation. Radiation-induced intestinal leakage of fluorescein isothiocyanate-conjugated dextran was examined in separate experiments.
  
  
  RESULTS
  Immunoneutralization of P-selectin decreased radiation-provoked platelet rolling by 87% and adhesion by 63%. Moreover, inhibition of PSGL-1 decreased platelet rolling and adhesion by 77% and 83%, respectively, in animals exposed to radiation. Similarly, inhibition of P-selectin and PSGL-1 decreased radiation-induced leukocyte rolling and adhesion by more than 84% and 90%, respectively, in the colon. In contrast, inhibition of P-selectin or PSGL-1 had no impact on radiation-induced intestinal leakage. In addition, systemic depletion of platelets and leukocytes did not affect intestinal barrier dysfunction in radiated animals.
  
  
  CONCLUSIONS
  This study demonstrates that radiation-provoked platelet and leukocyte accumulation are mediated in part by P-selectin and PSGL-1. Radiation-induced gut leakage, however, is independent of accumulation of platelets and leukocytes in the intestinal microvasculature.
authors.affiliation: Department of Surgery, Malmö, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Andrada
authors.initials: A
authors.lastname: Mihaescu
authors.forename: Charlotte
authors.initials: C
authors.lastname: Thornberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Santén
authors.forename: Sören
authors.initials: S
authors.lastname: Mattsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Jeppsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Thorlacius
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000528:radiation effects*; D002448:Cell Adhesion / Q000528:radiation effects; D002450:Cell Communication / Q000528:radiation effects; D003106:Colon / Q000098:blood supply / Q000276:immunology / Q000528:radiation effects*; D042783:Endothelial Cells / Q000528:radiation effects*; D007413:Intestinal Mucosa / Q000528:radiation effects; D007962:Leukocytes / Q000528:radiation effects; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000528:radiation effects; D019007:P-Selectin / Q000378:metabolism*; D011878:Radiotherapy / Q000009:adverse effects
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein