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

Ulrich G. Steidl, R. Haas, R. Kronenwett

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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-1β-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.

Original languageEnglish (US)
Pages (from-to)414-423
Number of pages10
JournalAnnals of Hematology
Volume79
Issue number8
DOIs
StatePublished - Jun 2000
Externally publishedYes

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Antisense Oligonucleotides
Intercellular Adhesion Molecule-1
Monocytes
Down-Regulation
Antisense Oligodeoxyribonucleotides
Endothelial Cells
Blood Cells
Leukocytes
Lymphocytes
Transendothelial and Transepithelial Migration
Oligodeoxyribonucleotides
Cell Adhesion Molecules
Interleukin-1
Transfection
Flow Cytometry
Anti-Inflammatory Agents
Ligands
Inflammation
Lipids

Keywords

  • Anti-sense oligonucleotides
  • Inflammation
  • Intercellular adhesion molecule 1
  • Monocytes
  • Trans-endothelial migration

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Intercellular adhesion molecule 1 on monocytes mediates adhesion as well as trans-endothelial migration and can be downregulated using antisense oligonucleotides",
abstract = "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-1β-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.",
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T1 - Intercellular adhesion molecule 1 on monocytes mediates adhesion as well as trans-endothelial migration and can be downregulated using antisense oligonucleotides

AU - Steidl, Ulrich G.

AU - Haas, R.

AU - Kronenwett, R.

PY - 2000/6

Y1 - 2000/6

N2 - 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-1β-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.

AB - 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-1β-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.

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