Comparative Studies of the Colonic In Situ Expression of Intercellular Adhesion Molecules (ICAM-1, -2, and -3), β2 Integrins (LFA-1, Mac-1, and p150,95), and PECAM-1 in Ulcerative Colitis and Crohn's Disease

Abstract

A dysregulated local immune defense with a constant influx of leukocytes provides a basis for continuous intestinal inflammation in ulcerative colitis (UC) and Crohn's disease (CD). Cell adhesion molecules are pivotal for the migration of leukocytes from the circulation toward the colonic epithelium. A study quantifying the cells expressing intercellular adhesion molecules (ICAMs), beta2 integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the colon was performed to illustrate the leukocyte migration pathway in inflammatory bowel disease. Serial colonic sections (10 UC, 10 CD, and 10 controls) were stained immunohistochemically for ICAM-1, ICAM-2, ICAM-3, CD11a, CD11b, CD18, and PECAM-1. Cell adhesion molecule expression was evaluated quantitatively with reference to topographic localization. In UC, polymorphonuclear leukocytes (PMNs) in contact with the crypt epithelium and in crypt abscesses expressed CD11b. CD tissue was characterized by CD11a-, CD11c-, and ICAM-1-expressing cells. ICAM-1 was detected on endothelial cells, leukocytes, and apical parts of epithelial membranes, whereas ICAM-2 was expressed on basal epithelial membranes. Most infiltrating leukocytes expressed ICAM-3, whereas perivascular mononuclear cells expressed PECAM-1. Interestingly, the epithelial basement membrane in UC stained for CD18. In conclusion, CD11b, CD18, and ICAM-2 seem to be important for PMN transepithelial migration in UC, whereas CD11a, CD11c, ICAM-1, and ICAM-3 seem central in leukocyte locomotion and aggregation in CD. Differentiated upregulation of cell adhesion molecules is suggested to be essential for the diversities between UC and CD.

Regulation of dextran sodium sulfate induced colitis by leukocyte beta 2 integrins

“…Several reports have previously identified leukocyte and endothelial cell adhesion molecules as potentially important regulators of leukocyte recruitment in human IBD and experimental colitis. 35,36 Studies have implicated endothelial cell ICAM-1 and MadCAM-1 along with leukocyte a 4 b 1 (VLA-4) and a 4 b 7 expression as primary mediators of leukocyte recruitment in colitis. [37][38][39][40] However, other reports have clearly documented increased expression of b 2 integrins, including LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), in Crohn's disease and ulcerative colitis suggesting that these molecules may also play an important role in governing chronic inflammation of the bowel.…”

The physiological roles of ICAM-1 and ICAM-2 in neutrophil migration into tissues

“…So far, neutrophil trans-epithelial migration is considered to be regulated by interaction of the neutrophil Mac-1 with the basolateral aspects of the epithelium [63], and further involves interaction of epithelial CD47 with the neutrophil signal regulatory protein (SIRP)-a [64,65] in some epithelia [66]. Although ICAM-1 is up-regulated in colonic specimen of ulcerative colitis and Crohn's disease patients [67] and is expressed by choroid plexus epithelial cells in the brain [68,69], it is exclusively confined to the apical side of the epithelium and therefore not available for receptor/ligand-mediated neutrophil migration from the basolateral to the luminal compartment.…”

Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

“…ICAM-1 is reported to be expressed at high levels in IBD patients and during experimental colitis (31,160). Its ligands are members of the ␤ 2 family of integrins (LFA-1, Mac-1, CD11c/CD18, CD11d/CD18) and interaction mediates firm adhesion of and extravasation of leukocytes.…”