HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print October 4, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.0605326v1 78/5/1175    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gupta, S. Articles by Elsner, J. Search for Related Content PubMed PubMed Citation Articles by Gupta, S. Articles by Elsner, J.

(Journal of Leukocyte Biology. 2005;78:1175-1184.)
© 2005 by Society for Leukocyte Biology

Cloning, expression, and functional characterization of cynomolgus monkey (Macaca fascicularis) CC chemokine receptor 1

Shipra Gupta^*,, Sandra Schulz-Maronde^*,, Christian Kutzleb, Rudolf Richter, Wolf-Georg Forssmann, Alexander Kapp^*, Ulf Forssmann^,1 and Jörn Elsner^*,,

^* Departments of Dermatology and Allergology and
Pharmacology and Toxicology and
IPF PharmaCeuticals GmbH, An-Institut, Hannover Medical School, Germany; and
Department of Dermatology and Allergology, Fachklinik Bad Bentheim, Germany

¹Correspondence: IPF PharmaCeuticals GmbH, An-Institut of Hannover Medical School, Feodor-Lynen-Strasse 31, 30625 Hannover, Germany. E-mail: u.forssmann{at}ipf-pharmaceuticals.de

The CC chemokine receptor 1 (CCR1) has emerged as a relevant factor contributing to inflammatory diseases such as allergic asthma. Commonly used animal models of allergic airway inflammation, especially murine models, have certain limitations. The elaborate, nonhuman, primate models of asthma display the highest comparability with the situation in humans. These models play an important role in the understanding of the pathogenesis of asthma. To improve the understanding in cynomolgus monkey models, we identified and characterized CCR1 in this nonhuman primate. Initially, we cloned the cynomolgus monkey CCR1 (cCCR1) gene, and the sequence analysis revealed high homology at the nucleotide (92%) and amino acid (88.4%) levels with its human counterpart. Human embryonic kidney 293 cells were stably transfected with cCCR1 and used in functional assays. Among those CCR1 ligands tested, CCL14(9-74) was most potent in the induction of intracellular Ca²⁺ fluxes as observed for human CCR1 (hCCR1). Complete cross-desensitization could be achieved between CCL14(9-74) and CCL15. However, CCL3 could not fully abrogate the response to the potent ligand CCL14(9-74). Competition-binding studies with radiolabeled CCL3 concordantly showed that CCL14(9-74) has a higher affinity to cCCR1 than hCCL3. Moreover, differential tissue-specific expression of cCCR1 was investigated by real-time quantitative polymerase chain reaction, displaying the highest levels in spleen. This study adds basic information needed for the evaluation of the role of CCR1 in the pathophysiology of asthma using the highly relevant cynomolgus monkey model and in addition, aids in the preclinical evaluation of potential novel drugs targeting CCR1.

Key Words: G protein-coupled receptor • asthma • animal model • gene • signal transduction

This article has been cited by other articles:

				S. Gupta, B. Fuchs, S. Schulz-Maronde, A. Heitland, S. E. Escher, M. Mack, H.-C. Tillmann, A. Braun, W.-G. Forssmann, J. Elsner, et al. Intravascular inactivation of CCR5 by n-Nonanoyl-CC chemokine ligand 14 and inhibition of allergic airway inflammation J. Leukoc. Biol., March 1, 2008; 83(3): 765 - 773. [Abstract] [Full Text] [PDF]