Document Detail

Dendritic cells distinguish individual chemokine signals through CCR7 and CXCR4.
MedLine Citation:
PMID:  21106854     Owner:  NLM     Status:  MEDLINE    
Dendritic cells (DCs) respond to chemotactic signals to migrate from sites of infection to secondary lymphoid organs where they initiate the adaptive immune response. The key chemokines directing their migration are CCL19, CCL21, and CXCL12, but how signals from these chemokines are integrated by migrating cells is poorly understood. Using a microfluidic device, we presented single and competing chemokine gradients to murine bone-marrow derived DCs in a controlled, time-invariant microenvironment. Experiments performed with counter-gradients revealed that CCL19 is 10-100-fold more potent than CCL21 or CXCL12. Interestingly, when the chemoattractive potencies of opposing gradients are matched, cells home to a central region in which the signals from multiple chemokines are balanced; in this region, cells are motile but display no net displacement. Actin and myosin inhibitors affected the speed of crawling but not directed motion, whereas pertussis toxin inhibited directed motion but not speed. These results provide fundamental insight into the processes that DCs use to migrate toward and position themselves within secondary lymphoid organs.
Brendon G Ricart; Beena John; Dooyoung Lee; Christopher A Hunter; Daniel A Hammer
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-24
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-21     Completed Date:  2011-01-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  53-61     Citation Subset:  AIM; IM    
Department of Chemical and Biomolecular Engineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
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MeSH Terms
Actins / antagonists & inhibitors,  physiology
Bone Marrow Cells / immunology,  metabolism
Cell Differentiation / immunology
Cells, Cultured
Chemokine CCL19 / physiology
Chemokine CXCL12 / physiology
Chemotaxis, Leukocyte / immunology
Dendritic Cells / cytology,  immunology*,  metabolism*
Lymphoid Tissue / cytology,  immunology,  metabolism
Mice, Inbred C57BL
Microfluidic Analytical Techniques* / methods
Myosins / antagonists & inhibitors,  physiology
Receptors, CCR7 / biosynthesis,  deficiency,  physiology*
Receptors, CXCR4 / biosynthesis,  physiology*
Signal Transduction / immunology*
Grant Support
Reg. No./Substance:
0/Actins; 0/CXCR4 protein, mouse; 0/Ccl19 protein, mouse; 0/Ccr7 protein, mouse; 0/Chemokine CCL19; 0/Chemokine CXCL12; 0/Cxcl12 protein, mouse; 0/Receptors, CCR7; 0/Receptors, CXCR4; EC

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