VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis.
OBJECTIVE
The molecular mechanisms responsible for leukocyte recruitment in experimental colitis are poorly understood. The aims of this study were to measure expression of endothelial intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and to determine their role in leukocyte recruitment in experimental colitis.


METHODS
Rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis and control rats were studied 1, 7, or 21 days after treatment. ICAM-1 and VCAM-1 expressions were measured by the double radiolabeled antibody technique. Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. Therapeutic effects of treatment with anti-VCAM-1 antibodies were also assessed.


RESULTS
Colonic endothelial ICAM-1 was constitutively expressed and did not increase in colitic animals. In contrast, constitutive expression of VCAM-1 was low but markedly increased (6-fold) 1 and 7 days after induction of colitis. Increased colonic expression of VCAM-1 paralleled macroscopic damage score, myeloperoxidase activity, and increased leukocyte adhesion in colonic venules. The latter was significantly decreased by immunoneutralization of ICAM-1 and completely abrogated by immunoneutralization of VCAM-1. Long-term administration of anti-VCAM-1 antibody resulted in significant attenuation of colitis.


CONCLUSIONS
Induction of colitis in rats by TNBS is followed by up-regulation of endothelial VCAM-1. VCAM-1 and constitutive ICAM-1 are major determinants of leukocyte recruitment to the inflamed intestine.
Sans
M
M
Department of Gastroenterology, Institut d'Investigacions Biomédiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
Panés
J
J
Ardite
E
E
Elizalde
J I
JI
Arce
Y
Y
Elena
M
M
Palacín
A
A
Fernández-Checa
J C
JC
Anderson
D C
DC
Lobb
R
R
Piqué
J M
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002448:Cell Adhesion; D003092:Colitis / Q000473:pathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*
D000911:Antibodies, Monoclonal; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014302:Trinitrobenzenesulfonic Acid