PMID- 12689946
OWN - NLM
STAT- MEDLINE
DCOM- 20030922
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 102
IP  - 3
DP  - 2003 Aug 1
TI  - Eotaxin-3 is a natural antagonist for CCR2 and exerts a repulsive effect on human 
      monocytes.
PG  - 789-94
AB  - Eotaxin-3 (CCL26) belongs to the group of CC chemokines that attract eosinophils, 
      basophils, and Th2 lymphocytes. Like eotaxin (CCL11) and eotaxin-2 (CCL24), 
      eotaxin-3 mediates its activity through CCR3. Here we show that eotaxin-3 also 
      binds to CCR2 on monocytes and CCR2-transfected cells. In contrast to monocyte 
      chemotactic protein 1 (MCP-1; CCL2), eotaxin-3 does not trigger intracellular 
      calcium mobilization, enzyme release, or phosphorylation of the mitogen-activated 
      protein (MAP) kinase ERK and induces a weak chemotaxis in monocytes. Instead, 
      eotaxin-3 inhibits MCP-1-mediated responses, thus acting as a natural antagonist 
      for CCR2. This study also demonstrates that eotaxin-3 promotes active movement of 
      monocytes away from a gradient of eotaxin-3 in vitro. This repellent effect is 
      amplified when an additional gradient of MCP-1 is applied, demonstrating that the 
      2 mechanisms are synergistic. Eotaxin-3 effects on monocytes are largely 
      abolished when cells are pretreated with MCP-1 or CCR2 antagonists. Like 
      MCP-1-mediated migration, repulsion is sensitive to Bordetella pertussis toxin, 
      indicating the involvement of Gi protein-coupled receptors. However, using 
      transfected cells expressing CCR2 we could not detect F-actin formation or an 
      active movement away induced by eotaxin-3, suggesting that either expression of a 
      single receptor type is not sufficient to mediate cell repulsion or that the used 
      transfected cell lines lack additional interaction molecules that are required 
      for reverse migration. Eotaxin-3 was expressed by vascular endothelial cells and 
      was essential for endothelial transmigration of eosinophils. Our data provide a 
      mechanism by which 2 chemokine gradients that are oriented in opposite directions 
      could cooperate in efficiently driving out monocytes from blood vessels into 
      tissue.
FAU - Ogilvie, Patricia
AU  - Ogilvie P
AD  - Institute for Research in Biomedicine, Via Vela 6, 6500 Bellinzona, Switzerland.
FAU - Paoletti, Samantha
AU  - Paoletti S
FAU - Clark-Lewis, Ian
AU  - Clark-Lewis I
FAU - Uguccioni, Mariagrazia
AU  - Uguccioni M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030410
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CCL26 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL26)
RN  - 0 (Chemokines, CC)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Chemokine CCL26
MH  - Chemokines, CC/metabolism/pharmacology/*physiology
MH  - Chemotaxis, Leukocyte/*drug effects
MH  - Humans
MH  - Inflammation/pathology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Monocytes/*cytology/drug effects
MH  - Protein Binding
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/*antagonists & inhibitors
MH  - Transfection
EDAT- 2003/04/12 05:00
MHDA- 2003/09/23 05:00
CRDT- 2003/04/12 05:00
PHST- 2003/04/12 05:00 [pubmed]
PHST- 2003/09/23 05:00 [medline]
PHST- 2003/04/12 05:00 [entrez]
AID - S0006-4971(20)50549-1 [pii]
AID - 10.1182/blood-2002-09-2773 [doi]
PST - ppublish
SO  - Blood. 2003 Aug 1;102(3):789-94. doi: 10.1182/blood-2002-09-2773. Epub 2003 Apr 
      10.