Intercellular adhesion molecule-1 (ICAM-1) deficiency protects mice against severe forms of experimentally induced colitis

ICAM-1 (CD54), the ligand for LFA-1 and Mac-1, is up-regulated during infla mmatory reaction on the activated vascular endothelium. To determine its ro le in intestinal inflammation, we induced acute experimental colitis in mic e with a deleted ICAM-1 gene, by feeding them with 3% dextran sodium sulpha te (DSS) in drinking water for 7 days. Chronic colitis was elicited by DSS similarly, followed by 2 weeks with water. In the acute phase of inflammati on, ICAM-1-deficient mice exhibited a significantly lower mortality rate (5 %) than control C57Bl/6J mice (35%). Control animals, but not the ICAM-1-de ficient mice, exhibited diarrhoea and rectal bleeding. Histological examina tion of large-bowel samples evaluated the intensity of inflammatory changes , and type and extent of mucosal lesions. In the acute phase, 33.3% of samp les from ICAM-1-deficient mice exhibited mucosal defects (flat and fissural ulcers), predominantly mild to moderate inflammatory infiltrate within the lamina propria mucosae and lower grades of mucosal lesions. Much stronger inflammatory changes were present in control animals, flat ulcers (sometime s multiple) and fissural ulcers being observed in 62.5% of samples. Mucosal inflammatory infiltrate was moderate to severe, typically with higher grad es of mucosal lesions. In chronic colitis, smaller inflammatory changes wer e found in the large bowel. The two mouse strains differed, the chronic col itis being accompanied by an increased serum level of anti-epithelial IgA a utoantibodies in C57Bl/6 control mice but not in ICAM-1-deficient mice. The se findings provide direct evidence of the participation of ICAM-1 molecule in the development of experimentally induced intestinal inflammation.