Intercellular adhesion molecule 1 on monocytes mediates adhesion as well as trans-endothelial migration and can be downregulated using antisense oligonucleotides

The intercellular adhesion molecule 1 (ICAM-1) on endothelial cells is invo lved in the recruitment of leukocytes to inflammatory sites. In contrast to ICAM-1 expression on endothelial cells, little is known about its function in leukocytes in inflammation. Using ICAM-1-directed anti-sense oligodeoxy ribonucleotides (ODNs), we examined the role of ICAM-1 expression on monocy tes and lymphocytes for adhesion and trans-endothelial migration. As determ ined by flow cytometry, a downregulation of the ICAM-1 expression of 50% wa s observed on peripheral blood mononuclear cells (PBMCs) after their transf ection with anti-sense ODNs using cationic lipids. The decrease in the leve l of ICAM-1 expression in PBMCs was associated with a 36% inhibition of adh esion to interleukin-1 beta-stimulated endothelial cells and a 40% reductio n of trans-endothelial migration. Gating on particular subsets of the PBMC, the downregulation of ICAM-1 and the functional effects could be ascribed to monocytes, while no significant inhibition was found for lymphocytes. Th is could be explained by differences in cellular ODN uptake. Since the liga nds of ICAM-1 are not expressed on endothelial cells, the results suggest a homotypic interaction among monocytes. In conclusion, in addition to ICAM- 1 expression on endothelial cells, ICAM-1 expression on monocytes mediates adhesion and transendothelial migration. This might be relevant for the cli nical use of ICAM-1-directed anti-sense ODNs for the treatment of inflammat ory diseases, because monocytes appear to be suitable target cells in which to achieve anti-inflammatory effects.