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I‐TAC/CXCL11 is a natural antagonist for CCR5
Author(s) -
Petkovic Vibor,
Moghini Christian,
Paoletti Samantha,
Uguccioni Mariagrazia,
Gerber Basil
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1103570
Subject(s) - cxcl14 , ccl5 , xcl2 , cxcl9 , ccl17 , biology , cxcl11 , cxcl10 , c c chemokine receptor type 6 , cxcr3 , microbiology and biotechnology , chemokine receptor ccr5 , cxc chemokine receptors , cc chemokine receptors , cxcl16 , chemokine receptor , chemokine , ccl7 , ccr3 , t cell , immunology , inflammation , il 2 receptor , immune system
The selective CXC chemokine receptor 3 (CXCR3) agonists, monokine induced by interferon‐γ (IFN‐ γ)/CXC chemokine ligand 9 (CXCL9), IFN‐inducible protein 10/CXCL10, and IFN‐inducible T cell α chemoattractant (I‐TAC)/CXCL11, attract CXCR3 + cells such as CD45RO + T lymphocytes, B cells, and natural killer cells. Further, all three chemokines are potent, natural antagonists for chemokine receptor 3 (CCR3) and feature defensin‐like, antimirobial activities. In this study, we show that I‐TAC, in addition to these effects, acts as an antagonist for CCR5. I‐TAC inhibited the binding of macrophage‐inflammatory protein‐1α (MIP‐1α)/CC chemokine ligand 3 (CCL3) to cells transfected with CCR5 and to monocytes. Furthermore, cell migration evoked by regulated on activation, normal T expressed and secreted (RANTES)/CCL5 and MIP‐1β/CCL4, the selective agonist of CCR5, was inhibited in transfected cells and monocytes, respectively. In two other functional assays, namely the release of free intracellular calcium and actin polymerization, I‐TAC reduced CCR5 activities to minimal levels. Sequence and structure analyses indicate a potential role for K17, K49, and Q51 of I‐TAC in CCR5 binding. Our results expand on the potential role of I‐TAC as a negative modulator in leukocyte migration and activation, as I‐TAC would specifically counteract the responses mediated by many “classical,” inflammatory chemokines that act not only via CCR3 but via CCR5 as well.