Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

J. Cell Sci. 116 (22): 4615-4628

Research Article

Potential role of MCP-1 in endothelial cell tight junction `opening': signaling via Rho and Rho kinase

Svetlana M. Stamatovic1, Richard F. Keep1,3, Steven L. Kunkel2, and Anuska V. Andjelkovic1,2,*

1 Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
2 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
3 Department of Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA

* Author for correspondence (e-mail: anuskaa{at}umich.edu)

Accepted for publication 8 July 2003.

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.

Key Words: MCP-1 • Tight junction • RhoA • Rho kinase • Brain endothelial permeability

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Effect of Monocyte Chemoattractant Protein-1/CC Chemokine Ligand 2 on Aqueous Humor Outflow Facility.
N. Tsuboi, T. Inoue, M. Kawai, M. Inoue-Mochita, T. Fujimoto, N. Awai-Kasaoka, A. Yoshida, and H. Tanihara (2012)
Invest. Ophthalmol. Vis. Sci. 53, 6702-6707
   Abstract »    Full Text »    PDF »
Relocalization of Junctional Adhesion Molecule A during Inflammatory Stimulation of Brain Endothelial Cells.
S. M. Stamatovic, N. Sladojevic, R. F. Keep, and A. V. Andjelkovic (2012)
Mol. Cell. Biol. 32, 3414-3427
   Abstract »    Full Text »    PDF »
HIV-1 Tat Triggers Nuclear Localization of ZO-1 via Rho Signaling and cAMP Response Element-Binding Protein Activation.
Y. Zhong, B. Zhang, S. Y. Eum, and M. Toborek (2012)
J. Neurosci. 32, 143-150
   Abstract »    Full Text »    PDF »
Exploring the Neuroimmunopharmacology of Opioids: An Integrative Review of Mechanisms of Central Immune Signaling and Their Implications for Opioid Analgesia.
M. R. Hutchinson, Y. Shavit, P. M. Grace, K. C. Rice, S. F. Maier, and L. R. Watkins (2011)
Pharmacol. Rev. 63, 772-810
   Abstract »    Full Text »    PDF »
Truncation of monocyte chemoattractant protein 1 by plasmin promotes blood-brain barrier disruption.
Y. Yao and S. E. Tsirka (2011)
J. Cell Sci. 124, 1486-1495
   Abstract »    Full Text »    PDF »
MCP-1/CCR2B-dependent loop upregulates MUC5AC and MUC5B in human airway epithelium.
M. E. Monzon, R. M. Forteza, and S. M. Casalino-Matsuda (2011)
Am J Physiol Lung Cell Mol Physiol 300, L204-L215
   Abstract »    Full Text »    PDF »
Functional SNP of ARHGEF10 confers risk of atherothrombotic stroke.
T. Matsushita, K. Ashikawa, K. Yonemoto, Y. Hirakawa, J. Hata, H. Amitani, Y. Doi, T. Ninomiya, T. Kitazono, S. Ibayashi, et al. (2010)
Hum. Mol. Genet. 19, 1137-1146
   Abstract »    Full Text »    PDF »
Monocyte Chemoattractant Proteins Mediate Myocardial Microvascular Dysfunction in Swine Renovascular Hypertension.
J. Lin, X. Zhu, A. R. Chade, K. L. Jordan, R. Lavi, E. Daghini, M. E. Gibson, A. Guglielmotti, A. Lerman, and L. O. Lerman (2009)
Arterioscler Thromb Vasc Biol 29, 1810-1816
   Abstract »    Full Text »    PDF »
Dengue Virus Pathogenesis: an Integrated View.
B. E. E. Martina, P. Koraka, and A. D. M. E. Osterhaus (2009)
Clin. Microbiol. Rev. 22, 564-581
   Abstract »    Full Text »    PDF »
Mouse Adenovirus Type 1-Induced Breakdown of the Blood-Brain Barrier.
L. E. Gralinski, S. L. Ashley, S. D. Dixon, and K. R. Spindler (2009)
J. Virol. 83, 9398-9410
   Abstract »    Full Text »    PDF »
Effect of the Monocyte Chemoattractant Protein-1/CC Chemokine Receptor 2 System on Nephrin Expression in Streptozotocin-Treated Mice and Human Cultured Podocytes.
E. Tarabra, S. Giunti, F. Barutta, G. Salvidio, D. Burt, G. Deferrari, R. Gambino, D. Vergola, S. Pinach, P. C. Perin, et al. (2009)
Diabetes 58, 2109-2118
   Abstract »    Full Text »    PDF »
Caveolae-mediated Internalization of Occludin and Claudin-5 during CCL2-induced Tight Junction Remodeling in Brain Endothelial Cells.
S. M. Stamatovic, R. F. Keep, M. M. Wang, I. Jankovic, and A. V. Andjelkovic (2009)
J. Biol. Chem. 284, 19053-19066
   Abstract »    Full Text »    PDF »
NAD(P)H Oxidase-Dependent Regulation of CCL2 Production during Retinal Inflammation.
W. Zhang, M. Rojas, B. Lilly, N.-T. Tsai, T. Lemtalsi, G. I. Liou, R. W. Caldwell, and R. B. Caldwell (2009)
Invest. Ophthalmol. Vis. Sci. 50, 3033-3040
   Abstract »    Full Text »    PDF »
Phosphorylation of GTP dissociation inhibitor by PKA negatively regulates RhoA.
J. Qiao, O. Holian, B.-S. Lee, F. Huang, J. Zhang, and H. Lum (2008)
Am J Physiol Cell Physiol 295, C1161-C1168
   Abstract »    Full Text »    PDF »
Control of Chemokine Gradients by the Retinal Pigment Epithelium.
G. Shi, A. Maminishkis, T. Banzon, S. Jalickee, R. Li, J. Hammer, and S. S. Miller (2008)
Invest. Ophthalmol. Vis. Sci. 49, 4620-4630
   Abstract »    Full Text »    PDF »
Endothelial EphA receptor stimulation increases lung vascular permeability.
J. Larson, S. Schomberg, W. Schroeder, and T. C. Carpenter (2008)
Am J Physiol Lung Cell Mol Physiol 295, L431-L439
   Abstract »    Full Text »    PDF »
Rho Kinase Inhibition in Severe Malaria: Thwarting Parasite-Induced Collateral Damage to Endothelia.
Z. Taoufiq, F. Gay, J. Balvanyos, L. Ciceron, M. Tefit, P. Lechat, and D. Mazier (2008)
The Journal of Infectious Disease 197, 1062-1073
   Abstract »    Full Text »    PDF »
Activation of Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) Suppresses Rho GTPases in Human Brain Microvascular Endothelial Cells and Inhibits Adhesion and Transendothelial Migration of HIV-1 Infected Monocytes.
S. H. Ramirez, D. Heilman, B. Morsey, R. Potula, J. Haorah, and Y. Persidsky (2008)
J. Immunol. 180, 1854-1865
   Abstract »    Full Text »    PDF »
Expression of CCR2 in Both Resident and Bone Marrow-Derived Microglia Plays a Critical Role in Neuropathic Pain.
J. Zhang, X. Q. Shi, S. Echeverry, J. S. Mogil, Y. De Koninck, and S. Rivest (2007)
J. Neurosci. 27, 12396-12406
   Abstract »    Full Text »    PDF »
CB2-receptor stimulation attenuates TNF-{alpha}-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion.
M. Rajesh, P. Mukhopadhyay, S. Batkai, G. Hasko, L. Liaudet, J. W. Huffman, A. Csiszar, Z. Ungvari, K. Mackie, S. Chatterjee, et al. (2007)
Am J Physiol Heart Circ Physiol 293, H2210-H2218
   Abstract »    Full Text »    PDF »
MK2 controls the level of negative feedback in the NF-{kappa}B pathway and is essential for vascular permeability and airway inflammation.
M. M. Gorska, Q. Liang, S. J. Stafford, N. Goplen, N. Dharajiya, L. Guo, S. Sur, M. Gaestel, and R. Alam (2007)
J. Exp. Med. 204, 1637-1652
   Abstract »    Full Text »    PDF »
Impaired tight junction sealing and precocious involution in mammary glands of PKN1 transgenic mice.
A. Fischer, H. Stuckas, M. Gluth, T. D. Russell, M. C. Rudolph, N. E. Beeman, S. Bachmann, S. Umemura, Y. Ohashi, M. C. Neville, et al. (2007)
J. Cell Sci. 120, 2272-2283
   Abstract »    Full Text »    PDF »
Alteration in the gene expression pattern of primary monocytes after adhesion to endothelial cells.
S. Thomas-Ecker, A. Lindecke, W. Hatzmann, C. Kaltschmidt, K. S. Zanker, and T. Dittmar (2007)
PNAS 104, 5539-5544
   Abstract »    Full Text »    PDF »
Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis.
A. W. Orr, R. Stockton, M. B. Simmers, J. M. Sanders, I. J. Sarembock, B. R. Blackman, and M. A. Schwartz (2007)
J. Cell Biol. 176, 719-727
   Abstract »    Full Text »    PDF »
Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis.
T. Nakazawa, T. Hisatomi, C. Nakazawa, K. Noda, K. Maruyama, H. She, A. Matsubara, S. Miyahara, S. Nakao, Y. Yin, et al. (2007)
PNAS 104, 2425-2430
   Abstract »    Full Text »    PDF »
MCP-1, a highly expressed chemokine in dengue haemorrhagic fever/dengue shock syndrome patients, may cause permeability change, possibly through reduced tight junctions of vascular endothelium cells.
Y.-R. Lee, M.-T. Liu, H.-Y. Lei, C.-C. Liu, J.-M. Wu, Y.-C. Tung, Y.-S. Lin, T.-M. Yeh, S.-H. Chen, and H.-S. Liu (2006)
J. Gen. Virol. 87, 3623-3630
   Abstract »    Full Text »    PDF »
CCL2 Regulates Angiogenesis via Activation of Ets-1 Transcription Factor.
S. M. Stamatovic, R. F. Keep, M. Mostarica-Stojkovic, and A. V. Andjelkovic (2006)
J. Immunol. 177, 2651-2661
   Abstract »    Full Text »    PDF »
Recent Evidence for an Involvement of Rho-Kinase in Cerebral Vascular Disease.
S. Chrissobolis and C. G. Sobey (2006)
Stroke 37, 2174-2180
   Abstract »    Full Text »    PDF »
ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability.
F. Wegmann, B. Petri, A. G. Khandoga, C. Moser, A. Khandoga, S. Volkery, H. Li, I. Nasdala, O. Brandau, R. Fassler, et al. (2006)
J. Exp. Med. 203, 1671-1677
   Abstract »    Full Text »    PDF »
Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE).
Y. Persidsky, D. Heilman, J. Haorah, M. Zelivyanskaya, R. Persidsky, G. A. Weber, H. Shimokawa, K. Kaibuchi, and T. Ikezu (2006)
Blood 107, 4770-4780
   Abstract »    Full Text »    PDF »
Protein Kinase C{alpha}-RhoA Cross-talk in CCL2-induced Alterations in Brain Endothelial Permeability.
S. M. Stamatovic, O. B. Dimitrijevic, R. F. Keep, and A. V. Andjelkovic (2006)
J. Biol. Chem. 281, 8379-8388
   Abstract »    Full Text »    PDF »
Endogenous NO Blockade Enhances Tissue Factor Expression via Increased Ca2+ Influx Through MCP-1 in Endothelial Cells by Monocyte Adhesion.
T. Sakamoto, T. Ishibashi, N. Sakamoto, K. Sugimoto, K. Egashira, H. Ohkawara, K. Nagata, K. Yokoyama, M. Kamioka, T. Ichiki, et al. (2005)
Arterioscler Thromb Vasc Biol 25, 2005-2011
   Abstract »    Full Text »    PDF »
Barriers built on claudins.
K. Turksen and T.-C. Troy (2004)
J. Cell Sci. 117, 2435-2447
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882