Role of P-selectin in radiation-induced intestinal inflammatory damage.
The aims of our study were to characterize the dose- and time-dependent changes in endothelial P-selectin expression and the role of this adhesion molecule as a mediator of radiation-induced inflammation. For that purpose, endothelial P-selectin expression was measured by the radiolabeled antibody technique in control and irradiated mice at 2, 6, and 24 hr following abdominal irradiation with 4 or 10 Gy; leukocyte endothelial cell interactions were assessed using intravital microscopy in intestinal venules following irradiation at the aforementioned doses and times in C57BL/6 and P-selectin-deficient mice. In wild-type mice, radiation induced a time- and dose-dependent up-regulation of P-selectin and a significant increase in the flux of rolling leukocytes 2 hr after irradiation. Irradiation induced a significant increase in leukocyte adhesion that was dose-dependent. Following irradiation, P-selectin-deficient mice did not show any increase in leukocyte rolling but did demonstrate a response in leukocyte adhesion similar to that of the wild-type mice. Radiation-induced dose-dependent histological inflammatory damage that did not differ between P-selectin-deficient and wild-type mice. We conclude that P-selectin is up-regulated following irradiation and is a key molecular determinant of leukocyte rolling but not leukocyte adhesion in this inflammatory condition. Therefore, isolated neutralization of this adhesion molecule is not an effective means for preventing radiation-induced inflammation.
Mollà
M
M
Department of Gastroenterology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pí i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Gironella
M
M
Salas
A
A
Miquel
R
R
Pérez-del-Pulgar
S
S
Conill
C
C
Engel
P
P
Biete
A
A
Piqué
J M
JM
Panés
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001772:Blood Cell Count; D002448:Cell Adhesion; D004307:Dose-Response Relationship, Radiation; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000528:radiation effects; D007249:Inflammation / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000528:radiation effects*; D007962:Leukocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000528:radiation effects; D019007:P-Selectin / Q000096:biosynthesis* / Q000502:physiology*; D011878:Radiotherapy / Q000009:adverse effects*; D013997:Time Factors; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D019007:P-Selectin