Relative roles of ICAM-1 and VCAM-1 in the pathogenesis of experimental radiation-induced intestinal inflammation.
OBJECTIVE
Cell adhesion molecules mediate leukocyte recruitment into the irradiated organs; modulation of this process may protect from radiation damage. Our objective was to characterize the requirement for intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in intestinal inflammatory response after abdominal irradiation.


METHODS
Endothelial ICAM-1 and VCAM-1 expression was determined using radiolabeled antibodies in mice 24 h and 14 days after irradiation with 10 Gy, or sham radiation. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy, and the function of ICAM-1 and VCAM-1 in this process by using blocking antibodies and ICAM-1(-/-) mice.


RESULTS
The number of adherent leukocytes significantly increased 24 h after irradiation and remained elevated at 14 days. Treatment with anti-ICAM-1 antibodies and ICAM-1 genetic deficiency significantly reduced leukocyte adhesion 24 h after irradiation. At 14 days after irradiation, both wild-type and ICAM-1(-/-) mice had an upregulation of VCAM-1, expression, and VCAM-1 immunoneutralization, but not ICAM-1 immunoneutralization, significantly reduced leukocyte adhesion. In ICAM-1(-/-) mice, regeneration of the intestinal epithelium was enhanced relative to wild-type mice.


CONCLUSIONS
ICAM-1 plays a key role in leukocyte recruitment at early time points after abdominal irradiation, whereas VCAM-1 is the main molecular determinant of leukocyte recruitment at late time points.
Mollà
Meritxell
M
Department of Gastroenterology, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Gironella
Meritxell
M
Miquel
Rosa
R
Tovar
Victoria
V
Engel
Pablo
P
Biete
Albert
A
Piqué
Josep M
JM
Panés
Julián
J
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004751:Enteritis / Q000097:blood / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D007422:Intestines / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1