Premium
Intravascular inactivation of CCR5 by n ‐Nonanoyl‐CC chemokine ligand 14 and inhibition of allergic airway inflammation
Author(s) -
Gupta Shipra,
Fuchs Barbara,
SchulzMaronde Sandra,
Heitland Aleksandra,
Escher Sylvia E.,
Mack Matthias,
Tillmann HannsChristian,
Braun Armin,
Forssmann WolfGeorg,
Elsner Jörn,
Forssmann Ulf
Publication year - 2008
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.0607429
Subject(s) - ccr1 , chemokine receptor , ccr3 , chemokine , cc chemokine receptors , inflammation , in vivo , receptor , allergic inflammation , immunology , biology , c c chemokine receptor type 6 , chemokine receptor ccr5 , microbiology and biotechnology , biochemistry
Modulation of leukocyte recruitment through intervention with chemokine receptors is an attractive, therapeutic strategy. Recently, we have shown that n‐Nonanoyl (NNY)‐CCL14 internalizes and desensitizes human (h)CCR3, resulting in the inactivation of eosinophils. In this study, we investigated the interaction of NNY‐CCL14 with CCR1 and CCR5 and the relevance of these NNY‐CCL14 receptors on its in vivo effects in allergic airway inflammation. NNY‐CCL14 has inactivating properties on CCR1 + and CCR5 + cell lines and primary leukocytes. It desensitizes hCCR1‐ and hCCR5‐mediated calcium release and internalizes these receptors from the cellular surface. Treatment of OVA‐sensitized BALB/c mice with NNY‐CCL14 resulted in reduced pulmonary inflammation. Above all, it is demonstrated that systemic treatment with NNY‐CCL14 down‐modulates CCR5 from the surface of lymphocytes in vivo. Although NNY‐CCL14 acts on murine lymphocytes and internalizes CCR5, it does not internalize CCR3 on mouse eosinophils, showing species selectivity regarding this particular receptor. Therefore, the inhibitory effects of NNY‐CCL14 in murine models of allergic airway inflammation can be assigned to its interaction with CCR5. The presented results substantiate the relevance of CCR5 as a target for allergic airway inflammation.