title: Influence of dose-rate on inflammatory damage and adhesion molecule expression after abdominal radiation in the rat.
abstract: OBJECTIVE
  The goal of this study was to assess the effects of two clinically relevant radiation dose-rates on endothelial adhesion molecule expression, inflammatory response, and microvascular dysfunction.
  
  
  METHODS
  Rats were irradiated with 10 Gy at low (0.9 Gy/min) or high (3 Gy/min) dose-rates. Control animals received sham irradiation. Leukocyte rolling, adhesion, emigration, and microvascular permeability were assessed in mesenteric venules by intravital microscopy 6 hours after irradiation. P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression were measured using radiolabeled monoclonal antibodies.
  
  
  RESULTS
  Low dose-rate (LDR) abdominal irradiation increased leukocyte adhesion compared with sham-irradiated animals, whereas high dose-rate (HDR) irradiation resulted in enhanced leukocyte rolling, adhesion, and emigration, compared with the LDR or with sham-irradiated rats. Both dose-rates increased microvascular permeability, although this effect was significantly greater after radiation with the high (8-fold) than the low (5-fold) dose-rate. HDR radiation induced significantly larger increments in P-selectin expression in splanchnic organs than LDR, whereas in most organs ICAM-1 expression was only upregulated by the HDR. Blockade of ICAM-1, but not P-selectin, abrogated leukocyte adhesion at both dose-rates.
  
  
  CONCLUSIONS
  The magnitude of upregulation of endothelial adhesion molecules, leukocyte recruitment, and endothelial barrier dysfunction elicited by radiation therapy is dependent on the dose-rate at which the radiation is delivered.
authors.affiliation: Gastroenterology Department, Institut Clínic de Malalties Digestives, IDIBAPS, Hospital Clínic, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Mollà
authors.forename: J
authors.initials: J
authors.lastname: Panés
authors.forename: M
authors.initials: M
authors.lastname: Casadevall
authors.forename: A
authors.initials: A
authors.lastname: Salas
authors.forename: C
authors.initials: C
authors.lastname: Conill
authors.forename: A
authors.initials: A
authors.lastname: Biete
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
authors.forename: J M
authors.initials: JM
authors.lastname: Piqué
mesh_terms: D000005:Abdomen; D000818:Animals; D002199:Capillary Permeability / Q000528:radiation effects*; D002448:Cell Adhesion / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D007249:Inflammation / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000528:radiation effects*; D008297:Male; D019007:P-Selectin / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1