PMID- 14576355
OWN - NLM
STAT- MEDLINE
DCOM- 20040608
LR  - 20220318
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 116
IP  - Pt 22
DP  - 2003 Nov 15
TI  - Potential role of MCP-1 in endothelial cell tight junction 'opening': signaling 
      via Rho and Rho kinase.
PG  - 4615-28
AB  - The expression of the monocyte chemoattractant protein-1 (MCP-1) receptor CCR2 by 
      brain endothelial cells suggests that MCP-1 may have other functions than purely 
      driving leukocyte migration into brain parenchyma during inflammation. This study 
      examines one of these potential novel roles of MCP-1 regulation of endothelial 
      permeability using primary cultures of mouse brain endothelial cells. MCP-1 
      induces reorganization of actin cytoskeleton (stress fiber formation) and 
      redistribution of tight junction proteins, ZO-1, ZO-2 occludin and claudin-5, 
      from the Triton X-100-soluble to the Triton X-100-insoluble fractions. These 
      morphological changes are associated with a decrease in transendothelial 
      electrical membrane resistance and an increase in [14C]inulin permeability. MCP-1 
      did not induce these events in brain endothelial cells prepared from mice 
      genotype CCR2-/-. The Rho kinase inhibitor Y27632 and inhibition of Rho (C3 
      exoenzyme, and dominant negative mutant of Rho, RhoT19N) prevented MCP-1-induced 
      stress fiber assembly, reorganization of tight junction proteins and alterations 
      in endothelial permeability. In all, this suggests that a small GTPase Rho and 
      Rho kinase have a pivotal role in MCP-1-induced junction disarrangement. These 
      data are the first to strongly suggest that MCP-1, via CCR2 present on brain 
      endothelial cells, contributes to increased brain endothelial permeability.
FAU - Stamatovic, Svetlana M
AU  - Stamatovic SM
AD  - Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 
      48109, USA.
FAU - Keep, Richard F
AU  - Keep RF
FAU - Kunkel, Steven L
AU  - Kunkel SL
FAU - Andjelkovic, Anuska V
AU  - Andjelkovic AV
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Claudin-5)
RN  - 0 (Cldn5 protein, mouse)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Occludin)
RN  - 0 (Ocln protein, mouse)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Tjp2 protein, mouse)
RN  - 0 (Zonula Occludens-2 Protein)
RN  - 0 (acute-phase protein rho)
RN  - 9002-93-1 (Octoxynol)
RN  - 9005-80-5 (Inulin)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Acute-Phase Proteins/*metabolism
MH  - Animals
MH  - Brain/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Claudin-5
MH  - Electric Impedance
MH  - Endothelial Cells/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Inulin/metabolism
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Microscopy, Fluorescence
MH  - Mutation
MH  - Occludin
MH  - Octoxynol/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Permeability/*drug effects
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/metabolism
MH  - Stress Fibers/metabolism
MH  - Tight Junctions/*metabolism
MH  - Zonula Occludens-2 Protein
MH  - rho-Associated Kinases
EDAT- 2003/10/25 05:00
MHDA- 2004/06/21 10:00
CRDT- 2003/10/25 05:00
PHST- 2003/10/25 05:00 [pubmed]
PHST- 2004/06/21 10:00 [medline]
PHST- 2003/10/25 05:00 [entrez]
AID - 116/22/4615 [pii]
AID - 10.1242/jcs.00755 [doi]
PST - ppublish
SO  - J Cell Sci. 2003 Nov 15;116(Pt 22):4615-28. doi: 10.1242/jcs.00755.