PMID- 12609829
OWN - NLM
STAT- MEDLINE
DCOM- 20040204
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 101
IP  - 12
DP  - 2003 Jun 15
TI  - CCR7 ligands induce rapid endocytosis in mature dendritic cells with concomitant 
      up-regulation of Cdc42 and Rac activities.
PG  - 4923-9
AB  - Although chemokines are well known to function in chemotaxis, additional roles 
      for these molecules in the immune system are not well understood. Dendritic cells 
      (DCs) developmentally regulate the expression of chemokine receptors to 
      facilitate their migration from the peripheral tissues to regional lymph nodes. 
      Expressions of CCR1 and CCR5 on immature DCs are down-regulated on maturation, 
      whereas CCR7 is selectively expressed on mature DCs. In the present study, we 
      examined the effects of CCL19 and CCL21, 2 CCR7 ligands, on endocytosis of 
      fluorescein isothiocyanate (FITC)-dextran by murine DCs. Both CCL19 and CCL21 
      markedly induced rapid uptake of FITC-dextran by mature DCs but not immature DCs. 
      In contrast, CCL3, a ligand of CCR1 and CCR5, induced rapid uptake of 
      FITC-dextran by immature DCs but not mature DCs. CCL19-induced endocytosis could 
      be completely blocked by Clostridium difficile toxin B, which inhibits the Rho 
      guanosine triphosphatase proteins, Rho, Rac, and Cdc42. This process was not 
      abrogated by Y-27632, a specific inhibitor of Rho-associated kinase. In addition, 
      CCL19 rapidly enhanced Cdc42 and Rac activity in mature DCs. These findings 
      demonstrate that certain chemokines induce rapid endocytosis in each relevant DC 
      population. It is suggested that CCR7 ligands activate Cdc42 and Rac, thereby 
      inducing the endocytosis in mature DCs.
FAU - Yanagawa, Yoshiki
AU  - Yanagawa Y
AD  - Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, 
      Sapporo, Japan.
FAU - Onoe, Kazunori
AU  - Onoe K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030227
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Albumins)
RN  - 0 (Amides)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Ccl19 protein, mouse)
RN  - 0 (Ccl21c protein, mouse)
RN  - 0 (Ccr7 protein, mouse)
RN  - 0 (Chemokine CCL19)
RN  - 0 (Chemokine CCL21)
RN  - 0 (Chemokines, CC)
RN  - 0 (Dextrans)
RN  - 0 (Mannans)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (fluorescein isothiocyanate dextran)
RN  - 0 (toxB protein, Clostridium difficile)
RN  - 138381-45-0 (Y 27632)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
SB  - IM
MH  - Albumins/metabolism
MH  - Amides/pharmacology
MH  - Animals
MH  - *Bacterial Proteins
MH  - Bacterial Toxins/pharmacology
MH  - Cell Line
MH  - Chemokine CCL19
MH  - Chemokine CCL21
MH  - Chemokines, CC/pharmacology
MH  - Dendritic Cells/*metabolism
MH  - Dextrans/metabolism
MH  - Endocytosis/*drug effects
MH  - Female
MH  - Fluorescein-5-isothiocyanate/*analogs & derivatives/metabolism
MH  - Mannans/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Pertussis Toxin/pharmacology
MH  - Pyridines/pharmacology
MH  - Receptors, CCR7
MH  - Receptors, Chemokine/*metabolism
MH  - Spleen/cytology
MH  - cdc42 GTP-Binding Protein/antagonists & inhibitors/*physiology
MH  - rac GTP-Binding Proteins/antagonists & inhibitors/*physiology
EDAT- 2003/03/01 04:00
MHDA- 2004/02/05 05:00
CRDT- 2003/03/01 04:00
PHST- 2003/03/01 04:00 [pubmed]
PHST- 2004/02/05 05:00 [medline]
PHST- 2003/03/01 04:00 [entrez]
AID - S0006-4971(20)50660-5 [pii]
AID - 10.1182/blood-2002-11-3474 [doi]
PST - ppublish
SO  - Blood. 2003 Jun 15;101(12):4923-9. doi: 10.1182/blood-2002-11-3474. Epub 2003 Feb 
      27.