PMID- 21106854
OWN - NLM
STAT- MEDLINE
DCOM- 20110127
LR  - 20101221
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 186
IP  - 1
DP  - 2011 Jan 1
TI  - Dendritic cells distinguish individual chemokine signals through CCR7 and CXCR4.
PG  - 53-61
LID - 10.4049/jimmunol.1002358 [doi]
AB  - 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.
FAU - Ricart, Brendon G
AU  - Ricart BG
AD  - Department of Chemical and Biomolecular Engineering, School of Engineering and 
      Applied Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
FAU - John, Beena
AU  - John B
FAU - Lee, Dooyoung
AU  - Lee D
FAU - Hunter, Christopher A
AU  - Hunter CA
FAU - Hammer, Daniel A
AU  - Hammer DA
LA  - eng
GR  - AI071302/AI/NIAID NIH HHS/United States
GR  - AI082292/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101124
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Actins)
RN  - 0 (CXCR4 protein, mouse)
RN  - 0 (Ccl19 protein, mouse)
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Chemokine CCL19)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Receptors, CXCR4)
RN  - EC 3.6.4.1 (Myosins)
SB  - IM
MH  - Actins/antagonists & inhibitors/physiology
MH  - Animals
MH  - Bone Marrow Cells/immunology/metabolism
MH  - Cell Differentiation/immunology
MH  - Cells, Cultured
MH  - Chemokine CCL19/physiology
MH  - Chemokine CXCL12/physiology
MH  - Chemotaxis, Leukocyte/immunology
MH  - Dendritic Cells/cytology/*immunology/*metabolism
MH  - Lymphoid Tissue/cytology/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Microfluidic Analytical Techniques/methods
MH  - Myosins/antagonists & inhibitors/physiology
MH  - Receptors, CCR7/biosynthesis/deficiency/*physiology
MH  - Receptors, CXCR4/biosynthesis/*physiology
MH  - Signal Transduction/*immunology
EDAT- 2010/11/26 06:00
MHDA- 2011/01/29 06:00
CRDT- 2010/11/26 06:00
PHST- 2010/11/26 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2011/01/29 06:00 [medline]
AID - jimmunol.1002358 [pii]
AID - 10.4049/jimmunol.1002358 [doi]
PST - ppublish
SO  - J Immunol. 2011 Jan 1;186(1):53-61. doi: 10.4049/jimmunol.1002358. Epub 2010 Nov 
      24.