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Cloning and characterization of a new intercellular adhesion molecule ICAM-R
R Vazeux1, P A Hoffman, J K Tomita
1ICOS Corporation, Bothell, Washington 98021.
Nature
|December 3, 1992
Summary
Researchers identified ICAM-R, a new intercellular adhesion molecule. This molecule, related to ICAM-1 and ICAM-2, binds to LFA-1 on leukocytes, distinct from endothelial cells.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Intercellular adhesion molecules (ICAMs) like ICAM-1 and ICAM-2, along with beta 2 integrins (leukointegrins), are crucial for leukocyte and endothelial cell adhesion, vital for immune function.
- Complete blocking of leukocyte function-associated antigen LFA-1-dependent adhesion using antibodies against ICAM-1 and ICAM-2 suggests the existence of other LFA-1 ligands, such as the previously identified ICAM-3.
Purpose of the Study:
- To molecularly clone and characterize a novel member of the ICAM family, designated ICAM-R.
- To investigate the structural and functional relationship of ICAM-R to ICAM-1 and ICAM-2.
- To determine the expression pattern and ligand-binding properties of ICAM-R.
Main Methods:
- Molecular cloning of the complementary DNA (cDNA) encoding ICAM-R.
- Analysis of the ICAM-R protein sequence and domain structure.
- Determination of the molecular weight (M(r)) of the mature cell-surface form of ICAM-R.
- Comparison of protein sequence identity with ICAM-1 and ICAM-2.
- Assessment of ICAM-R expression on different cell types (leukocytes and endothelial cells) in resting and activated states.
- Functional assay to confirm ICAM-R as a ligand for CD11a/LFA-1.
Main Results:
- A novel ICAM family member, ICAM-R, was molecularly cloned. Its cDNA is 1,781 base pairs long, encoding a protein with five extracellular immunoglobulin-family type domains.
- The mature ICAM-R protein exhibits a cell type-specific molecular weight ranging from 116 to 140K.
- Protein sequence identity between ICAM-R and ICAM-1 is 48%, and with ICAM-2 is 31%, with variations across domains.
- ICAM-R is highly expressed on resting leukocytes of all lineages but not on resting or cytokine-activated endothelial cells, differentiating its expression from ICAM-1 and ICAM-2.
- ICAM-R functions as a ligand for the beta 2-integrin CD11a/LFA-1, similar to ICAM-1 and ICAM-2.
Conclusions:
- ICAM-R represents a newly identified member of the ICAM family with distinct structural and expression characteristics.
- The unique expression pattern of ICAM-R on leukocytes suggests a specific role in leukocyte adhesion and immune responses.
- ICAM-R's ability to bind LFA-1 further implicates it in leukocyte trafficking and interactions within the immune system.
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