title: VCAM-1 and ICAM-1 mediate leukocyte-endothelial cell adhesion in rat experimental colitis.
abstract: 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.
authors: Department of Gastroenterology, Institut d'Investigacions Biomédiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
authors: M
authors: M
authors: Sans
authors: J
authors: J
authors: Panés
authors: E
authors: E
authors: Ardite
authors: J I
authors: JI
authors: Elizalde
authors: Y
authors: Y
authors: Arce
authors: M
authors: M
authors: Elena
authors: A
authors: A
authors: Palacín
authors: J C
authors: JC
authors: Fernández-Checa
authors: D C
authors: DC
authors: Anderson
authors: R
authors: R
authors: Lobb
authors: J M
authors: JM
authors: Piqué
mesh_terms: 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*
chemical_list: D000911:Antibodies, Monoclonal; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014302:Trinitrobenzenesulfonic Acid