PMID- 10209033
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 145
IP  - 2
DP  - 1999 Apr 19
TI  - Visualization of chemokine binding sites on human brain microvessels.
PG  - 403-12
AB  - The chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage 
      inflammatory protein-1alpha (MIP-1alpha) aid in directing leukocytes to specific 
      locales within the brain and spinal cord during central nervous system 
      inflammation. However, it remains unclear how these chemokines exert their 
      actions across a vascular barrier, raising speculation that interaction with 
      endothelial cells might be required. Therefore, experiments were performed to 
      determine whether binding domains for these chemokines exist along the outer 
      surface of brain microvessels, a feature that could potentially relay chemokine 
      signals from brain to blood. Using a biotinylated chemokine binding assay with 
      confocal microscopy and three-dimensional image reconstruction, spatially 
      resolved binding sites for MCP-1 and MIP-alpha around human brain microvessels 
      were revealed for the first time. Binding of labeled MCP-1 and MIP-1alpha could 
      be inhibited by unlabeled homologous but not heterologous chemokine, and was 
      independent of the presence of heparan sulfate, laminin, or collagen in the 
      subendothelial matrix. This is the first evidence of specific and separate 
      binding domains for MCP-1 and MIP-1alpha on the parenchymal surface of 
      microvessels, and highlights the prospect that specific interactions of 
      chemokines with microvascular elements influence the extent and course of central 
      nervous system inflammation.
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 - Spencer, D D
AU  - Spencer DD
FAU - Pachter, J S
AU  - Pachter JS
LA  - eng
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 Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Recombinant Proteins)
RN  - 0 (macrophage inflammatory protein 1alpha receptor)
SB  - IM
MH  - Binding, Competitive
MH  - Cerebral Cortex/*blood supply
MH  - *Cerebrovascular Circulation
MH  - Chemokine CCL2/*metabolism
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Kinetics
MH  - Macrophage Inflammatory Proteins/*metabolism
MH  - Microcirculation/immunology/*physiology
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/analysis/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Substrate Specificity
MH  - Temporal Lobe/*blood supply
PMC - PMC2133113
EDAT- 1999/04/20 00:00
MHDA- 1999/04/20 00:01
PMCR- 1999/10/19
CRDT- 1999/04/20 00:00
PHST- 1999/04/20 00:00 [pubmed]
PHST- 1999/04/20 00:01 [medline]
PHST- 1999/04/20 00:00 [entrez]
PHST- 1999/10/19 00:00 [pmc-release]
AID - 10.1083/jcb.145.2.403 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Apr 19;145(2):403-12. doi: 10.1083/jcb.145.2.403.