Cloning and pharmacological characterization of CCR7, CCL21 and CCL19 from Macaca fascicularis

被引：3
作者：
Moxley, Rachel [1 ]
Day, Elizabeth [1 ]
Brown, Kate [1 ]
Mahnke, Marion [2 ]
Zurini, Mauro [2 ]
Schmitz, Rita [2 ]
Jones, Carol E. [1 ]
Jarai, Gabor [1 ]
机构：
[1] Novartis Horsham Reseach Ctr, Horsham RH12 5AB, W Sussex, England
[2] Novartis Pharma AG, Novartis Biol Ctr, Antibody Ctr Excellence, CH-4002 Basel, Switzerland
来源：
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | 2009年 / 37卷 / 3-4期
关键词：
Macaca fascicularis; CCR7; CCL21; CCL19; LYMPHOID-ORGAN CHEMOKINE; HIGH-AFFINITY BINDING; ALLERGIC INFLAMMATION; DENDRITIC CELLS; RECEPTOR CCR7; MICE; ACTIVATION; EXPRESSION; FIBROBLASTS; MIP-3-BETA;
D O I：
10.1016/j.ejps.2009.02.013
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The chemokine receptor CCR7 and its ligands CCL19 and CCL21 play an important role in lymphocyte homing and have also been associated with inflammatory, allergic and lung disorders. Cloning of the cynomolgus monkey genes encoding CCR7, CCL19 and CCL21 revealed 93-97% sequence identity of the deduced proteins with their respective human homologs. In chemotaxis assays, B300-19 cells transfected with the cynmolgus (c) CCR7 receptor migrated in response to cCCL19 and cCCL21 in a dose-dependent manner with EC50 values of 324 +/- 188 nM and 247 +/- 29 nM, respectively. cCCL19 and cCCL21 also elicited calcium responses in stable cell CHO-K1 lines expressing the cCCR7 receptor with EC50 values of 227 +/- 4 nM and 484 +/- 163 nM, respectively. Although both human (h) CCL19 and hCCL21 elicited increases in intracellular calcium at the cCCR7 receptor, hCCL19 almost completely inhibited subsequent stimulation by hCCL21 whilst hCCL21 failed to inhibit subsequent stimulation by hCCL19. These results identify novel cynomolgus monkey genes and provide a model system for pre-clinical studies of potential drug candidates. (C) 2009 Elsevier B.V. All rights reserved.
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收藏
页码：264 / 271
页数：8
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