The DOI matches its Crossref record; 117 of the 119 references it cites were found in a registry or an index.
Potential role of MCP-1 in endothelial cell tight junction `opening': signaling via Rho and Rho kinase
Abstract
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.
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Metadata
- Authors
- Stamatovic, S. M., Keep, R. F., Kunkel, S. L., & Andjelkovic, A. V.
- Affiliations
- University of Michigan (US)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2003-11-15
- Volume
- 116
- Issue
- 22
- Pages
- 4615-4628
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1968099474
- Cited by
- 381
- References
- 119
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 14 · 2023: 20 · 2022: 15 · 2021: 19 · 2020: 20 · 2019: 21 · 2018: 19 · 2017: 17 · 2016: 19 · 2015: 20 · 2014: 16 · 2013: 20 · 2012: 21
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- MCP-1, CCR2, brain endothelial cells, endothelial permeability, tight junctions, Rho kinase, Rho GTPases, actin cytoskeleton remodeling, stress fibers, ZO-1, occludin, claudin-5, transendothelial electrical resistance, leukocyte migration
- MeSH terms
- Acute-Phase Proteins, Animals, Brain, Cells, Cultured, Inulin, Membrane Proteins, Microscopy, Fluorescence, Mutation, Permeability, Electric Impedance, Protein Serine-Threonine Kinases, Octoxynol, Mice, Knockout, Chemokine CCL2, Tight Junctions, Receptors, Chemokine, Oligonucleotide Array Sequence Analysis, Stress Fibers, Endothelial Cells, Intracellular Signaling Peptides and Proteins, Mice, Receptors, CCR2, rho-Associated Kinases, Claudin-5, Occludin, Zonula Occludens-2 Protein
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