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Centre National de la Recherche Scientifique, Unité Propre de Recherche 0415, Cell Biology Department, Institut Cochin de Génétique Moléculaire, Université Paris VII, Paris, France;
Endothelial and Epithelial Cell Biology, Institute of Ophthalmology, University College London, London, United Kingdom;
Laboratoire Physico-Chimie Curie, Institut Curie-Centre National de la Recherche Scientifique, Unité Mixte de Recherche 168, Paris, France; and
§
Neurotech SA, Immeuble Génopole-Industries, Evry, France
Endothelium of the cerebral blood vessels, which constitutes the
blood-brain barrier, controls adhesion and trafficking of leukocytes
into the brain. Investigating signaling pathways triggered by the
engagement of adhesion molecules expressed on brain endothelial cells
using two rat brain endothelial cell lines (RBE4 and GP8), we report in
this paper that ICAM-1 cross-linking induces a sustained tyrosine
phosphorylation of the phosphatidylinositol-phospholipase C
(PLC)
1, with a concomitant increase in both
inositol phosphate production and intracellular calcium concentration.
Our results suggest that PLC are responsible, via a calcium- and
protein kinase C (PKC)-dependent pathway, for
p60Src activation and tyrosine phosphorylation
of the p60Src substrate, cortactin. PKCs are
also required for tyrosine phosphorylation of the
cytoskeleton-associated proteins, focal adhesion kinase and paxillin,
but not for ICAM-1-coupled p130Cas
phosphorylation. PKC’s activation is also necessary for stress fiber
formation induced by ICAM-1 cross-linking. Finally, cell pretreatment
with intracellular calcium chelator or PKC inhibitors significantly
diminishes transmonolayer migration of activated T lymphocytes, without
affecting their adhesion to brain endothelial cells. In summary, our
data demonstrate that ICAM-1 cross-linking induces calcium signaling
which, via PKCs, mediates phosphorylation of actin-associated proteins
and cytoskeletal rearrangement in brain endothelial cell lines. Our
results also indicate that these calcium-mediated intracellular events
are essential for lymphocyte migration through the blood-brain
barrier.
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G. Cepinskas, J. Savickiene, C. V. Ionescu, and P. R. Kvietys PMN transendothelial migration decreases nuclear NF{kappa}B in IL-1{beta}-activated endothelial cells: role of PECAM-1 J. Cell Biol., May 12, 2003; 161(3): 641 - 651. [Abstract] [Full Text] [PDF]
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T.-H. Lee, H. K. Avraham, S. Jiang, and S. Avraham Vascular Endothelial Growth Factor Modulates the Transendothelial Migration of MDA-MB-231 Breast Cancer Cells through Regulation of Brain Microvascular Endothelial Cell Permeability J. Biol. Chem., February 7, 2003; 278(7): 5277 - 5284. [Abstract] [Full Text] [PDF]
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P. W. Thompson, A. M. Randi, and A. J. Ridley Intercellular Adhesion Molecule (ICAM)-1, But Not ICAM-2, Activates RhoA and Stimulates c-fos and rhoA Transcription in Endothelial Cells J. Immunol., July 15, 2002; 169(2): 1007 - 1013. [Abstract] [Full Text] [PDF]
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H. A. Edens, B. P. Levi, D. L. Jaye, S. Walsh, T. A. Reaves, J. R. Turner, A. Nusrat, and C. A. Parkos Neutrophil Transepithelial Migration: Evidence for Sequential, Contact-Dependent Signaling Events and Enhanced Paracellular Permeability Independent of Transjunctional Migration J. Immunol., July 1, 2002; 169(1): 476 - 486. [Abstract] [Full Text] [PDF]
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N. Q. Liu, A. S. Lossinsky, W. Popik, X. Li, C. Gujuluva, B. Kriederman, J. Roberts, T. Pushkarsky, M. Bukrinsky, M. Witte, et al. Human Immunodeficiency Virus Type 1 Enters Brain Microvascular Endothelia by Macropinocytosis Dependent on Lipid Rafts and the Mitogen-Activated Protein Kinase Signaling Pathway J. Virol., June 5, 2002; 76(13): 6689 - 6700. [Abstract] [Full Text] [PDF]
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H. E. de Vries, J. J. A. Hendriks, H. Honing, C. R. de Lavalette, S. M. A. van der Pol, E. Hooijberg, C. D. Dijkstra, and T. K. van den Berg Signal-Regulatory Protein {alpha}-CD47 Interactions Are Required for the Transmigration of Monocytes Across Cerebral Endothelium J. Immunol., June 1, 2002; 168(11): 5832 - 5839. [Abstract] [Full Text] [PDF]
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C. E. Walters, G. Pryce, D. J. R. Hankey, S. M. Sebti, A. D. Hamilton, D. Baker, J. Greenwood, and P. Adamson Inhibition of Rho GTPases with Protein Prenyltransferase Inhibitors Prevents Leukocyte Recruitment to the Central Nervous System and Attenuates Clinical Signs of Disease in an Animal Model of Multiple Sclerosis J. Immunol., April 15, 2002; 168(8): 4087 - 4094. [Abstract] [Full Text] [PDF]
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J. D. van Buul, C. Voermans, V. van den Berg, E. C. Anthony, F. P. J. Mul, S. van Wetering, C. E. van der Schoot, and P. L. Hordijk Migration of Human Hematopoietic Progenitor Cells Across Bone Marrow Endothelium Is Regulated by Vascular Endothelial Cadherin J. Immunol., January 15, 2002; 168(2): 588 - 596. [Abstract] [Full Text] [PDF]
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S. K. Shaw, P. S. Bamba, B. N. Perkins, and F. W. Luscinskas Real-Time Imaging of Vascular Endothelial-Cadherin During Leukocyte Transmigration Across Endothelium J. Immunol., August 15, 2001; 167(4): 2323 - 2330. [Abstract] [Full Text] [PDF]
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K. Natarajan, N. C. Sahoo, and K. V. S. Rao Signal Thresholds and Modular Synergy During Expression of Costimulatory Molecules in B Lymphocytes J. Immunol., July 1, 2001; 167(1): 114 - 122. [Abstract] [Full Text] [PDF]
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 C.-D. Jun, M. Shimaoka, C. V. Carman, J. Takagi, and T. A. Springer Dimerization and the effectiveness of ICAM-1 in mediating LFA-1-dependent adhesion PNAS, June 5, 2001; 98(12): 6830 - 6835. [Abstract] [Full Text] [PDF]
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Q. Wang and C. M. Doerschuk The p38 Mitogen-Activated Protein Kinase Mediates Cytoskeletal Remodeling in Pulmonary Microvascular Endothelial Cells Upon Intracellular Adhesion Molecule-1 Ligation J. Immunol., June 1, 2001; 166(11): 6877 - 6884. [Abstract] [Full Text] [PDF]
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C. Amos, I. A. Romero, C. Schultze, J. Rousell, J. D. Pearson, J. Greenwood, and P. Adamson Cross-Linking of Brain Endothelial Intercellular Adhesion Molecule (ICAM)-1 Induces Association of ICAM-1 With Detergent-Insoluble Cytoskeletal Fraction Arterioscler. Thromb. Vasc. Biol., May 1, 2001; 21(5): 810 - 816. [Abstract] [Full Text] [PDF]
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