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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2648-2656. Prepublished online as a Blood First Edition Paper on July 21, 2008; DOI 10.1182/blood-2008-04-149039. This Article Full Text (PDF) All Versions of this Article: blood-2008-04-149039v1 112/7/2648    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Loos, T. Articles by Proost, P. Search for Related Content PubMed PubMed Citation Articles by Loos, T. Articles by Proost, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 7, 2008 Accepted July 10, 2008 Citrullination of CXCL10 and CXCL11 by peptidylarginine deiminase: a naturally occurring posttranslational modification of chemokines and new dimension of immunoregulation Tamara Loos, Anneleen Mortier, Mieke Gouwy, Isabelle Ronsse, Willy Put, Jean-Pierre Lenaerts, Jo Van Damme, and Paul Proost* Laboratory of Molecular Immunology, Rega Institute, K.U.Leuven, Leuven, Belgium * Corresponding author; email: paul.proost{at}rega.kuleuven.be. Interactions between chemokines and enzymes are vital in immunoregulation. Structural protein citrullination by peptidylarginine deiminase (PAD) has been associated with autoimmunity. In this report, we identified a novel naturally occurring posttranslational modification of chemokines, i.e. the deimination of arginine at position 5 into citrulline of CXC chemokine ligand 10 (CXCL10) by rabbit PAD and human PAD2. Citrullination reduced ( tenfold) the chemoattracting and signaling capacity of CXCL10 for CXC chemokine receptor 3 (CXCR3) transfectants, however, did not affect CXCR3 binding. On T lymphocytes, though, citrullinated CXCL10 remained active, but was again weaker than authentic CXCL10. PAD was also able to convert CXCL11, causing an impairment of CXCR3 signaling and T cell activation, though less pronounced than for CXCL10. Similarly, receptor binding properties of CXCL11 were not altered by citrullination. However, deimination decreased heparin binding properties of both CXCL10 and CXCL11. Overall, chemokines are the first immune modulators reported of being functionally modified by citrullination. These data provide new structure-function dimensions for chemokines in leukocyte mobilization, disclosing an anti-inflammatory role for PAD. Additionally, since citrullination has severe consequences for chemokine biology, this invites to reassess the involvement and impact of PAD and citrullinated peptides in inflammation, autoimmunity and hematological disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Loos, G. Opdenakker, J. Van Damme, and P. Proost Citrullination of CXCL8 increases this chemokine's ability to mobilize neutrophils into the blood circulation Haematologica, October 1, 2009; 94(10): 1346 - 1353. [Abstract] [Full Text] [PDF] S. Struyf, S. Noppen, T. Loos, A. Mortier, M. Gouwy, H. Verbeke, D. Huskens, S. Luangsay, M. Parmentier, K. Geboes, et al. Citrullination of CXCL12 Differentially Reduces CXCR4 and CXCR7 Binding with Loss of Inflammatory and Anti-HIV-1 Activity via CXCR4 J. Immunol., January 1, 2009; 182(1): 666 - 674. [Abstract] [Full Text] [PDF]

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