PMID- 11032879
OWN - NLM
STAT- MEDLINE
DCOM- 20001109
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 75
IP  - 5
DP  - 2000 Nov
TI  - Characterization of binding sites for chemokines MCP-1 and MIP-1alpha on human 
      brain microvessels.
PG  - 1898-906
AB  - The presence of binding sites for the beta chemokines monocyte chemoattractant 
      protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) has 
      recently been identified on human brain microvessels. We extend these findings in 
      this report to reveal that such sites exemplify characteristics of the recognized 
      major receptors for MCP-1 and MIP-1alpha: CCR2, and CCR1 and CCR5, respectively. 
      Specifically, labeled MCP-1 binding to isolated brain microvessels was inhibited 
      by unlabeled MCP-1 and MCP-3, the latter another CCR2 ligand, but not by 
      MIP-1alpha. Inhibition of labeled MIP-1alpha binding was achieved with unlabeled 
      MIP-1alpha and RANTES, the latter a beta chemokine that binds to both CCR1 and 
      CCR5, but not by MCP-1. Labeled MIP-1alpha binding was also antagonized by 
      unlabeled MCP-3, which is also recognized by CCR1, and MIP-1beta, which is a 
      ligand for CCR5. Labeled MCP-1 and MIP-1alpha were further observed to be 
      internalized within the endothelial cells of brain microvessels, following their 
      binding to the microvascular surface at 37 degrees C. Additionally, exposure of 
      microvessels to unlabeled MCP-1 or MIP-1alpha was accompanied by the initial loss 
      and subsequent recovery of surface binding sites for these chemokines, which 
      occurred on a time scale consistent with ligand-induced endocytosis and 
      recycling. These collective features bear striking similarity to those that 
      characterize interactions of MCP-1 and MIP-1alpha with their receptors on 
      leukocytes and underscore the concept of cognate chemokine receptors on brain 
      microvascular endothelium.
FAU - Andjelkovic, A V
AU  - Andjelkovic AV
AD  - Blood-Brain Barrier Laboratory, Department of Pharmacology, University of 
      Connecticut Health Center, Farmington, Connecticut 06030, USA.
FAU - Pachter, J S
AU  - Pachter JS
LA  - eng
GR  - MH54718/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  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (CCL7 protein, human)
RN  - 0 (CCR1 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokine CCL7)
RN  - 0 (Cytokines)
RN  - 0 (Ligands)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Monocyte Chemoattractant Proteins)
RN  - 0 (Receptors, CCR1)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Adult
MH  - Binding Sites
MH  - Binding, Competitive/drug effects
MH  - Brain/*blood supply/metabolism
MH  - Chemokine CCL2/*metabolism/pharmacology
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Chemokine CCL7
MH  - *Cytokines
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Ligands
MH  - Macrophage Inflammatory Proteins/*metabolism
MH  - Microcirculation/metabolism
MH  - Monocyte Chemoattractant Proteins/pharmacology
MH  - Receptors, CCR1
MH  - Receptors, CCR2
MH  - Receptors, CCR5/metabolism
MH  - Receptors, Chemokine/metabolism
EDAT- 2000/10/18 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/18 11:00
PHST- 2000/10/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/18 11:00 [entrez]
AID - 10.1046/j.1471-4159.2000.0751898.x [doi]
PST - ppublish
SO  - J Neurochem. 2000 Nov;75(5):1898-906. doi: 10.1046/j.1471-4159.2000.0751898.x.