Document Detail

Dipeptidyl peptidase IV (CD26) on T cells cleaves the CXC chemokine CXCL11 (I-TAC) and abolishes the stimulating but not the desensitizing potential of the chemokine.
MedLine Citation:
PMID:  12101279     Owner:  NLM     Status:  MEDLINE    
Dipeptidyl peptidase IV (DPP IV/CD26) is a costimulatory molecule as well as a protease highly expressed on T cells. Purified DPP IV has been recognized to inactivate peptide hormones, neuropeptides, and some chemokines by cleavage behind a proline residue at the penultimate N-terminal amino acid position. Here, we identified another substrate for DPP IV among the chemokine family: the interferon-inducible T cell alpha chemoattractant (I-TAC/CXCL11). Using a specific DPP IV inhibitor, we demonstrate that DPP IV is responsible for the cleavage of the chemokine by PHA/IL-2-treated T cells. As PHA/IL-2-treated T cells also express the CXCL11 receptor (CXCR3), we investigated whether truncation of CXCL11 would modulate its biological activity for these cells. Truncated CXCL11 [CXCL11(3-73)] had an eightfold reduced potential to bind and to regulate CXCR3, but was completely inactive in calcium flux and chemotaxis assays. However, consistent with its reduced but still considerable ability to down-regulate CXCR3, truncated CXCL11 desensitized T cell chemotaxis in response to the intact chemokine. Hence, CXCL11-induced T cell recruitment may be regulated by DPP IV-mediated proteolytic inactivation of CXCL11 and furthermore by desensitization of T cells via the degradation product CXCL11(3-73).
Andreas Ludwig; Florian Schiemann; Rolf Mentlein; Buko Lindner; Ernst Brandt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  72     ISSN:  0741-5400     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-08     Completed Date:  2002-08-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  183-91     Citation Subset:  IM    
Department of Immunology and Cell Biology, Forschungszentrum Borstel, Parkallee 22, D-23845 Borstel, Germany.
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MeSH Terms
Antigens, CD26 / metabolism*
Calcium / metabolism
Cells, Cultured
Chemokine CXCL11
Chemokines, CXC / metabolism*,  pharmacology
Chemotaxis, Leukocyte
Dose-Response Relationship, Immunologic
Lymphocyte Activation
Receptors, CXCR3
Receptors, Chemokine / metabolism
T-Lymphocytes / enzymology*,  immunology
Reg. No./Substance:
0/CXCL11 protein, human; 0/CXCR3 protein, human; 0/Chemokine CXCL11; 0/Chemokines, CXC; 0/Receptors, CXCR3; 0/Receptors, Chemokine; 7440-70-2/Calcium; EC, CD26

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