PMID- 12149218
OWN - NLM
STAT- MEDLINE
DCOM- 20020912
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 100
IP  - 4
DP  - 2002 Aug 15
TI  - Prostaglandin E2 is a key factor for CCR7 surface expression and migration of 
      monocyte-derived dendritic cells.
PG  - 1354-61
AB  - Dendritic cells (DCs) are potent antigen-presenting cells that are able to 
      initiate and modulate immune responses and are hence exploited as cellular 
      vaccines for immunotherapy. Their capacity to migrate from peripheral tissues to 
      the T-cell areas of draining lymph nodes is crucial for the priming of T 
      lymphocytes. In this study, we investigated how the maturation of human 
      monocyte-derived DCs (MoDCs) by several different stimuli under serum-free 
      conditions affected their T-cell stimulatory function, cytokine secretion, and 
      migratory behavior. Surprisingly, we found that for all maturation stimuli 
      tested, the addition of prostaglandin E2 (PGE2) was required for effective 
      migration of MoDCs toward the lymph node-derived chemokines CCL19 (EBI1 ligand 
      chemokine/macrophage inflammatory protein--3beta) and CCL21 (secondary lymphoid 
      tissue chemokine [SLC]/6Ckine). Costimulation with PGE2 enhanced the expression 
      of the CCL19/CCL21 receptor CCR7 on the cell surface of MoDCs when they were 
      matured with soluble CD40 ligand or proinflammatory cytokines, but did not affect 
      CCR7 expression of polyI:C-stimulated MoDCs. The effects of PGE2 on MoDCs were 
      mediated through increased cyclic adenosine monophosphate by 2 of the known PGE2 
      receptors, EP2 and EP4, which are expressed and down-regulated after PGE2 binding 
      in these cells. In conclusion, our results suggest that signals provided by the 
      proinflammatory mediator PGE2 are crucial for MoDCs to acquire potent T-helper 
      cell stimulatory capacity and substantial chemotactic responsiveness to lymph 
      node-derived chemokines. This is a new and important parameter for the 
      preparation of MoDCs as cellular vaccines in tumor immunotherapy. (Blood. 
      2002;100:1354-1361)
FAU - Scandella, Elke
AU  - Scandella E
AD  - Research Department and the Oncology Department, Cantonal Hospital St Gallen, 
      Switzerland.
FAU - Men, Ying
AU  - Men Y
FAU - Gillessen, Silke
AU  - Gillessen S
FAU - Forster, Reinhold
AU  - Forster R
FAU - Groettrup, Marcus
AU  - Groettrup M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CCL19 protein, human)
RN  - 0 (CCL21 protein, human)
RN  - 0 (CCR7 protein, human)
RN  - 0 (Chemokine CCL19)
RN  - 0 (Chemokine CCL21)
RN  - 0 (Chemokines, CC)
RN  - 0 (Cytokines)
RN  - 0 (PTGER2 protein, human)
RN  - 0 (PTGER4 protein, human)
RN  - 0 (Receptors, CCR7)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Receptors, Prostaglandin E)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - 0 (Receptors, Prostaglandin E, EP4 Subtype)
RN  - E0399OZS9N (Cyclic AMP)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Chemokine CCL19
MH  - Chemokine CCL21
MH  - Chemokines, CC
MH  - Chemotaxis/*drug effects
MH  - Coculture Techniques
MH  - Cyclic AMP/metabolism
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*physiology
MH  - Dinoprostone/*pharmacology
MH  - Gene Expression/*drug effects
MH  - Humans
MH  - Monocytes/physiology
MH  - Phenotype
MH  - Receptors, CCR7
MH  - Receptors, Chemokine/*genetics
MH  - Receptors, Prostaglandin E/genetics
MH  - Receptors, Prostaglandin E, EP2 Subtype
MH  - Receptors, Prostaglandin E, EP4 Subtype
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes
EDAT- 2002/08/01 10:00
MHDA- 2002/09/13 10:01
CRDT- 2002/08/01 10:00
PHST- 2002/08/01 10:00 [pubmed]
PHST- 2002/09/13 10:01 [medline]
PHST- 2002/08/01 10:00 [entrez]
AID - S0006-4971(20)59329-4 [pii]
AID - 10.1182/blood-2001-11-0017 [doi]
PST - ppublish
SO  - Blood. 2002 Aug 15;100(4):1354-61. doi: 10.1182/blood-2001-11-0017.