Title: CD13/aminopeptidase N-processed I-TAC/CXCL11 has reduced CXCR3 and CXCR7 binding and signaling properties that result in impaired lymphocyte chemotaxis and reduced inhibition of endothelial cell migration
Authors: Proost, Paul ×
Mortier, Anneleen
Loos, Tamara
Vandercappellen, Jo
Gouwy, Mieke
Ronsse, Isabelle
Schutyser, Evemie
Put, Willy
Parmentier, Marc
Struyf, Sofie
Van Damme, Jozef #
Issue Date: Jan-2008
Conference: Keystone Symposium on "Chemokines and Chemokine Receptors" location:Keystone, CO, U.S.A. date:13-18 January 2008
Abstract: Lecture Abstract: Fibroblasts and peripheral blood-derived mononuclear leukocytes (PBMC) were induced with interferon- (IFN-) and Toll-like receptor ligands (TLR). Natural truncated CXCL11 variants missing up to 6 amino acids were identified after chromatographic purification of the fibroblast- and PBMC-derived conditioned media. The myeloid cell marker and metalloprotease CD13/aminopeptidase N, in combination with CD26/dipeptidyl peptidase IV, rapidly processed CXCL11, but not IL-8/CXCL8. The truncated CXCL11 isoforms had reduced binding and signaling properties and impaired chemotactic activity on lymphocytes and CXCR3 or CXCR7 transfected CHO cells. CXCL11 that was processed by CD13 failed to induce an intracellular calcium increase but was still able to bind and desensitized CXCR3 for signaling induced with intact CXCL11. Although CXCL11 efficiently bound to CXCR7, no signaling (increase of intracellular calcium concentrations or ERK1/2 or Akt phosphorylation) could be detected on CXCR7-CHO cells that were treated with CXCL11. In addition, CXCL11 that was treated with CD26/DPP IV failed to attract lymphocytes but still inhibited microvascular endothelial cell (HMVEC) migration in accordance with previous observations in angiogenesis assays with CD26-truncated CXCL9 and CXCL10. However, upon further processing of CXCL11 by CD13 the inhibition of HMVEC migration significantly reduced. Taken together, CD26 processing of CXCR3 ligands during inflammation or cancer reduces the number of infiltrating leukocytes without altering the anti-angiogenic activity of these chemokines. Further processing of CXCL11 by CD13 reduces its anti-angiogenic activity and may lead to a more angiogenic environment.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory of Molecular Immunology (Rega Institute)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.


All items in Lirias are protected by copyright, with all rights reserved.