Abstract：
:The chemokine receptor CCR7 is crucial for migration of mature dendritic cells (DC) directed toward secondary lymphoid organs; however, there is little knowledge about the function of the homeostatic chemokine receptor CXCR4 in DC and its contribution to directional migration of DC during inflammation. By comparing the impact of chemokine receptor engagement on mature DC we found that the CCR7 ligand CCL19 holds a stronger chemotactic potency than the CXCR4 ligand CXCL12. Moreover, CCL19 elicited rapid, steep and long-lasting mobilization of intracellular calcium in individual cells and induced intense phosphorylation of extracellular signal-regulated kinase 1/2 and protein kinase B, while the intracellular signals elicited by CXCL12 were in part distinct and significantly weaker. Analysis of chemokine receptor expression revealed that although CCR7 and CXCR4 were expressed by a similar percentage of DC, the mean fluorescence intensity of CCR7 was up to six times higher, suggesting a higher receptor density. Based on these correlations we propose that the type of chemokine signal in conjunction with the expression and functional activity of the respective chemokine receptor is also determining the migration rate and potency of a chemotactic response in mature DC. In conclusion, our data support the fundamental role of CCR7 for rapidly guiding DC toward secondary lymphoid organs at an extra- and intracellular molecular level and on the contrary render CXCR4 a weaker contributor to directional migration of DC during inflammation.
journal_name
Immunologyjournal_title
Immunologyauthors
Humrich JY,Humrich JH,Averbeck M,Thumann P,Termeer C,Kämpgen E,Schuler G,Jenne Ldoi
10.1111/j.1365-2567.2005.02292.xkeywords:
subject
Has Abstractpub_date
2006-02-01 00:00:00pages
238-47issue
2eissn
0019-2805issn
1365-2567pii
IMM2292journal_volume
117pub_type
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