Document Detail

Hyaluronan induces cell death in activated T cells through CD44.
MedLine Citation:
PMID:  18981124     Owner:  NLM     Status:  MEDLINE    
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.
Brian Ruffell; Pauline Johnson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  181     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-04     Completed Date:  2008-12-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7044-54     Citation Subset:  AIM; IM    
Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
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MeSH Terms
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
Hyaluronic Acid / immunology,  metabolism*
In Situ Nick-End Labeling
Jurkat Cells
Lymphocyte Activation / immunology
Mice, Mutant Strains
Protein Binding
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes / immunology,  metabolism*
Reg. No./Substance:
0/Antigens, CD44; 0/Antigens, CD95; 0/CD44 protein, human; 0/Fas Ligand Protein; 9004-61-9/Hyaluronic Acid; 9007-28-7/Chondroitin Sulfates

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