PMID- 11717355
OWN - NLM
STAT- MEDLINE
DCOM- 20020111
LR  - 20240420
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 21
IP  - 23
DP  - 2001 Dec 1
TI  - The chemokine receptor CCR2 mediates the binding and internalization of monocyte 
      chemoattractant protein-1 along brain microvessels.
PG  - 9214-23
AB  - Previous results from this laboratory revealed the presence of high-affinity 
      saturable binding sites for monocyte chemoattractant protein-1 (MCP-1) along 
      human brain microvessels (Andjelkovic et al., 1999; Andjelkovic and Pachter, 
      2000), which suggested that CC chemokine receptor 2 (CCR2), the recognized 
      receptor for this chemokine, was expressed by the brain microvascular 
      endothelium. To test the role of CCR2 directly in mediating MCP-1 interactions 
      with the brain microvasculature, we assessed MCP-1 binding activity in murine 
      brain microvessels isolated from wild-type mice and from CCR2 (-/-) mice 
      engineered to lack this receptor. Results demonstrate that MCP-1 binding is 
      greatly attenuated in microvessels prepared from CCR2 (-/-) mice compared with 
      wild-type controls. Moreover, microvessels from wild-type mice exhibited 
      MCP-1-induced downmodulation in MCP-1 binding and a recovery of binding activity 
      that was not dependent on de novo protein synthesis. Furthermore, MCP-1 was shown 
      to be internalized within wild-type microvessels, but not within microvessels 
      obtained from CCR2 (-/-) mice, additionally demonstrating that CCR2 is obligatory 
      for MCP-1 endocytosis. Last, internalization of MCP-1, but not transferrin, was 
      observed to be inhibited by disruption of caveolae. Internalized MCP-1 also 
      colocalized at some sites with caveolin-1, a major protein of caveolae, implying 
      that this chemokine is endocytosed, in part, via nonclathrin-coated vesicles. 
      These results prompt consideration that MCP-1 signals may be relayed across the 
      blood-brain barrier by highly specialized interactions of this chemokine with its 
      cognate receptor, CCR2, along brain microvascular endothelial cells.
FAU - Dzenko, K A
AU  - Dzenko KA
AD  - Blood-Brain Barrier Laboratory, Department of Pharmacology, University of 
      Connecticut Health Center, Farmington, Connecticut 06030, USA.
FAU - Andjelkovic, A V
AU  - Andjelkovic AV
FAU - Kuziel, W A
AU  - Kuziel WA
FAU - Pachter, J S
AU  - Pachter JS
LA  - eng
GR  - R01 MH054718/MH/NIMH NIH HHS/United States
GR  - 1RO1-MH54718-01A1/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (CCR2 protein, human)
RN  - 0 (Cav1 protein, mouse)
RN  - 0 (Caveolin 1)
RN  - 0 (Caveolins)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (Ligands)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Transferrin)
RN  - 87Z59R7D14 (Filipin)
SB  - IM
MH  - Animals
MH  - Binding, Competitive/physiology
MH  - Brain/*blood supply
MH  - Caveolae/drug effects/metabolism
MH  - Caveolin 1
MH  - Caveolins/metabolism
MH  - Chemokine CCL2/*metabolism
MH  - Chemokines/metabolism
MH  - Crosses, Genetic
MH  - Down-Regulation
MH  - Endocytosis/drug effects/physiology
MH  - Endothelium, Vascular/cytology/drug effects/*metabolism
MH  - Filipin/pharmacology
MH  - In Vitro Techniques
MH  - Ligands
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Microcirculation/drug effects/*metabolism
MH  - Protein Binding/physiology
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/deficiency/genetics/*metabolism
MH  - Temperature
MH  - Transferrin/metabolism
PMC - PMC6763923
EDAT- 2001/11/22 10:00
MHDA- 2002/01/12 10:01
PMCR- 2002/06/01
CRDT- 2001/11/22 10:00
PHST- 2001/11/22 10:00 [pubmed]
PHST- 2002/01/12 10:01 [medline]
PHST- 2001/11/22 10:00 [entrez]
PHST- 2002/06/01 00:00 [pmc-release]
AID - 21/23/9214 [pii]
AID - 5846 [pii]
AID - 10.1523/JNEUROSCI.21-23-09214.2001 [doi]
PST - ppublish
SO  - J Neurosci. 2001 Dec 1;21(23):9214-23. doi: 10.1523/JNEUROSCI.21-23-09214.2001.