| Hyaluronan induces cell death in activated T cells through CD44. | |
MedLine Citation:
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PMID: 18981124 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the immune system, leukocyte activation induces CD44 to bind hyaluronan, a component of the extracellular matrix. Here we used gain and loss of hyaluronan-binding mutants of CD44 to examine the consequence of hyaluronan binding in T cells. Jurkat T cells transfected with CD44 mutated at S180, which prevented the addition of chondroitin sulfate, displayed constitutively high levels of hyaluronan binding. These cells were more susceptible to activation-induced cell death, whereas cells expressing a CD44 mutant unable to bind hyaluronan (R41A) were resistant to cell death. In TCR or PMA activated Jurkat T cells, hyaluronan induced rapid cell death. This depended on the level of hyaluronan binding by the cell, and the amount and size of hyaluronan. High molecular mass hyaluronan had the greatest effect and cell death occurred independently of Fas and caspase activation. In splenic T cells, high hyaluronan binding occurred in a subpopulation of cells undergoing activation-induced cell death. In addition, hyaluronan induced cell death in approximately 10% of reactivated splenic T cells when Fas-dependent apoptosis was prevented by Ab blocking or in Fas negative MRL/lpr T cells. This demonstrates that hyaluronan can induce cell death in activated, high hyaluronan binding T cells via a Fas-independent mechanism. |
Authors:
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Brian Ruffell; Pauline Johnson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 181 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-04 Completed Date: 2008-12-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 7044-54 Citation Subset: AIM; IM |
Affiliation:
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Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD44 / genetics, immunology, metabolism* Antigens, CD95 / immunology, metabolism Blotting, Western Cell Death / immunology* Chondroitin Sulfates / immunology, metabolism Fas Ligand Protein / immunology, metabolism Flow Cytometry Humans Hyaluronic Acid / immunology, metabolism* Immunoprecipitation In Situ Nick-End Labeling Jurkat Cells Lymphocyte Activation / immunology Mice Mice, Mutant Strains Protein Binding Reverse Transcriptase Polymerase Chain Reaction T-Lymphocytes / immunology, metabolism* Transfection |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD44; 0/Antigens, CD95; 0/CD44 protein, human; 0/Fas Ligand Protein; 9004-61-9/Hyaluronic Acid; 9007-28-7/Chondroitin Sulfates |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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