DNA aptamers block L-selectin function in vivo. Inhibition of human lymphocyte trafficking in SCID mice
| Autor: | Y F Chang, I Albinana, M C Willis, Brian Hicke, S Ringquist, L Moon-McDermott, C K Lynott, Tim Fitzwater, Susan Jennings, H L Han, David Parma, Andrea Koenig, Ajit Varki, R F Bargatze, S R Watson, Nissi Varki |
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| Rok vydání: | 1996 |
| Předmět: |
Aptamer
Deoxyribonucleotides Lewis X Antigen Mice SCID Biology Ligands Mice chemistry.chemical_compound In vivo Cell Adhesion Animals Lymphocytes Cloning Molecular L-Selectin Cell adhesion Binding Sites General Medicine Flow Cytometry Leukocyte extravasation Molecular biology DNA-Binding Proteins Spectrometry Fluorescence Sialyl-Lewis X chemistry biology.protein Calcium L-selectin Selectin Systematic evolution of ligands by exponential enrichment Protein Binding Research Article |
| Zdroj: | Journal of Clinical Investigation. 98:2688-2692 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci119092 |
| Popis: | Selectins participate in the initial events leading to leukocyte extravasation from the blood into tissues. Thus the selectins have generated much interest as targets for antiinflammatory agents. Therapeutic molecules based on the monomeric carbohydrate ligand sialyl Lewis X (SLe(X)) have low affinities and are not specific for a given selectin. Using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technology, we have generated aptamers specific for L-selectin that require divalent cations for binding and have low nanomolar affinity. In vitro, the deoxyoligonucleotides inhibit L-selectin binding to immobilized SLe(X) in static assays and inhibit L-selectin-mediated rolling of human lymphocytes and neutrophils on cytokine-activated endothelial cells in flow-based assays. These aptamers also block L-selectin-dependent lymphocyte trafficking in vivo, indicating their potential utility as therapeutics. |
| Databáze: | OpenAIRE |
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