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Blood, 1 July 2007, Vol. 110, No. 1, pp. 37-44. Prepublished online as a Blood First Edition Paper on March 15, 2007; DOI 10.1182/blood-2006-10-049072. This Article Full Text (PDF) All Versions of this Article: blood-2006-10-049072v1 110/1/37    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 Proost, P. Articles by Van Damme, J. Search for Related Content PubMed PubMed Citation Articles by Proost, P. Articles by Van Damme, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 2, 2006 Accepted March 8, 2007 Proteolytic processing of CXCL11 by CD13/aminopeptidase N impairs CXCR3 and CXCR7 binding and signalling and reduces lymphocyte and endothelial cell migration Paul Proost*, Anneleen Mortier, Tamara Loos, Jo Vandercappellen, Mieke Gouwy, Isabelle Ronsse, Evemie Schutyser, Willy Put, Marc Parmentier, Sofie Struyf, and Jo Van Damme Laboratory of Molecular Immunology, Rega Institute, University of Leuven, Leuven, Belgium IRIBHN, Universite Libre de Bruxelles, Brussels, Belgium * Corresponding author; email: paul.proost{at}rega.kuleuven.be. CXCR3 ligands were secreted by tissue fibroblasts and peripheral blood-derived mononuclear leukocytes in reponse to interferon- (IFN-) and Toll-like receptor ligands (TLR). Subsequent purification and identification revealed the presence of truncated CXCL11 variants missing up to 6 amino acids. In combination with CD26/dipeptidyl peptidase IV, the metalloprotease aminopeptidase N (APN), identical to the myeloid cell marker CD13, rapidly processed CXCL11, but not CXCL8, to generate truncated CXCL11 forms. Truncated CXCL11 had reduced binding, signalling and chemotactic properties for lymphocytes and CXCR3 or CXCR7 transfected cells. CD13/APN-truncated CXCL11 failed to induce an intracellular calcium increase but was still able to bind and desensitize CXCR3 for intact CXCL11 signalling. CXCL11 efficiently bound to CXCR7, but neither intact nor truncated CXCL11 were able to induce calcium signalling or ERK1/2 or Akt phosphorylation through CXCR7. CD26-truncated CXCL11 failed to attract lymphocytes but still inhibited microvascular endothelial cell (HMVEC) migration. However, further processing of CXCL11 by CD13 results in significant reduction of inhibition of HMVEC migration. Taken together, during inflammation or cancer CXCL11 processing by CD13 may lead to a reduced number of tumor-infiltrating lymphocytes and in a more angiogenic environment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] A. Doucet, G. S. Butler, D. Rodriguez, A. Prudova, and C. M. Overall Metadegradomics: Toward in Vivo Quantitative Degradomics of Proteolytic Post-translational Modifications of the Cancer Proteome Mol. Cell. Proteomics, October 1, 2008; 7(10): 1925 - 1951. [Abstract] [Full Text] [PDF] T. Loos, A. Mortier, M. Gouwy, I. Ronsse, W. Put, J.-P. Lenaerts, J. Van Damme, and P. Proost Citrullination of CXCL10 and CXCL11 by peptidylarginine deiminase: a naturally occurring posttranslational modification of chemokines and new dimension of immunoregulation Blood, October 1, 2008; 112(7): 2648 - 2656. [Abstract] [Full Text] [PDF] P. Proost, T. Loos, A. Mortier, E. Schutyser, M. Gouwy, S. Noppen, C. Dillen, I. Ronsse, R. Conings, S. Struyf, et al. Citrullination of CXCL8 by peptidylarginine deiminase alters receptor usage, prevents proteolysis, and dampens tissue inflammation J. Exp. Med., September 1, 2008; 205(9): 2085 - 2097. [Abstract] [Full Text] [PDF] J. H. Cox, R. A. Dean, C. R. Roberts, and C. M. Overall Matrix Metalloproteinase Processing of CXCL11/I-TAC Results in Loss of Chemoattractant Activity and Altered Glycosaminoglycan Binding J. Biol. Chem., July 11, 2008; 283(28): 19389 - 19399. [Abstract] [Full Text] [PDF] R. Ji, C. M. Lee, L. W. Gonzales, Y. Yang, M. O. Aksoy, P. Wang, E. Brailoiu, N. Dun, M. T. Hurford, and S. G. Kelsen Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1187 - L1196. [Abstract] [Full Text] [PDF] H. Dohner Implication of the Molecular Characterization of Acute Myeloid Leukemia Hematology, January 1, 2007; 2007(1): 412 - 419. [Abstract] [Full Text] [PDF]

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