Intercellular adhesion molecule 1 activation induces tyrosine phosphorylation of the cytoskeleton-associated protein cortactin in brain microvessel endothelial cells
Inflammatory diseases of the central nervous system, such as multiple sclerosis or experimental autoimmune encephalomyelitis, are characterized by adhesion of lymphocytes on cerebral microvascular endothelium, followed by transendothelial migration into the brain parenchyma. T lymphocyte adhesion to...
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Veröffentlicht in: | The Journal of biological chemistry 1994-04, Vol.269 (17), p.12536-12540 |
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Zusammenfassung: | Inflammatory diseases of the central nervous system, such as multiple sclerosis or experimental autoimmune encephalomyelitis,
are characterized by adhesion of lymphocytes on cerebral microvascular endothelium, followed by transendothelial migration
into the brain parenchyma. T lymphocyte adhesion to vascular endothelial cells is mediated by several types of adhesion molecules,
including the integrin leukocyte function-associated molecule 1 and its endothelial counter receptor intercellular adhesion
molecule 1 (ICAM-1), of the immunoglobulin superfamily. In order to understand the molecular mechanisms that support lymphocyte
extravasation, we intended to investigate a putative role of ICAM-1 in signal transduction in brain microvessel endothelial
cells. Here we describe, using a well differentiated rat brain endothelial cell line (RBE4 cells), that ICAM-1 activation
by a specific monoclonal antibody, or by syngeneic encephalitogenic T cells, induces tyrosine phosphorylation of several proteins
together with stimulation of the tyrosine kinase p60src activity. One of the major tyrosine-phosphorylated proteins, of 85
kDa, has been identified by immunoprecipitation and immunoblotting, as the recently described actin-binding protein, p60src
substrate, cortactin. These findings demonstrate that ICAM-1 activation transduces signals in brain endothelial cells, which
may lead to cytoskeleton changes and transendothelial migration of lymphocytes into the brain. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)99908-4 |