Influence of dose-rate on inflammatory damage and adhesion molecule expression after abdominal radiation in the rat.
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.
Mollà
M
M
Gastroenterology Department, Institut Clínic de Malalties Digestives, IDIBAPS, Hospital Clínic, Barcelona, Spain.
Panés
J
J
Casadevall
M
M
Salas
A
A
Conill
C
C
Biete
A
A
Anderson
D C
DC
Granger
D N
DN
Piqué
J M
JM
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
D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1