Intercellular adhesion molecular 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 involved 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 oligodeoxyribonucleotides (ODNs), we examined the role of ICAM-1 expression on monocytes and lymphocytes for adhesion and trans-endothelial migration. As determined by flow cytometry, a downregulation of the ICAM-1 expression of 50% was observed on peripheral blood mononuclear cells (PBMCs) after their transfection with anti-sense ODNs using cationic lipids. The decrease in the level of ICAM-1 expression in PBMCs was associated with a 36% inhibition of adhesion to interleukin-1beta-stimulated endothelial cells and a 40% reduction 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. This could be explained by differences in cellular ODN uptake. Since the ligands 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 clinical use of ICAM-1-directed anti-sense ODNs for the treatment of inflammatory diseases, because monocytes appear to be suitable target cells in which to achieve anti-inflammatory effects.
Steidl
U
U
Klinik für Hämatologie, Onkologie und klinische Immunologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Haas
R
R
Kronenwett
R
R
D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*
D016376:Oligonucleotides, Antisense; D018799:Intercellular Adhesion Molecule-1