Abstract
CD154, a member of the tumor necrosis factor-alpha family, has recently been implicated in the pathophysiology of vascular diseases. Indeed, blockade of CD154 by neutralizing antibodies or genetic disruption in mice prevents atherosclerosis and atherothrombosis. CD154 is believed to interact mainly via the CD40 receptor, however, it has also been found to bind with alphaIIbbeta3 integrin and so induces platelet activation. Moreover, we (and others) have recently identified the integrins alpha5beta1 and Mac-1 as novel CD154 receptors expressed on many cell types. Here, we illustrate the various functional features of these molecules, while describing the increasingly important role of CD40 in CD154-associated vascular pathologies such as atherosclerosis and atherothrombosis.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology*
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Antibodies, Monoclonal / therapeutic use
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Atherosclerosis / immunology*
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Atherosclerosis / pathology
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Atherosclerosis / physiopathology
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Atherosclerosis / therapy*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / pathology
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CD40 Antigens / immunology
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CD40 Antigens / metabolism
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CD40 Ligand / antagonists & inhibitors*
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CD40 Ligand / genetics
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CD40 Ligand / immunology
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CD40 Ligand / metabolism*
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Humans
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Immunotherapy*
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Integrin alpha5beta1 / immunology
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Integrin alpha5beta1 / metabolism
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Macrophage-1 Antigen / immunology
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Macrophage-1 Antigen / metabolism
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Mice
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Neovascularization, Pathologic / immunology
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Neovascularization, Pathologic / therapy
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Platelet Activation
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Platelet Glycoprotein GPIIb-IIIa Complex / immunology
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Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
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Signal Transduction / immunology
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Vasa Vasorum / immunology
Substances
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Antibodies, Monoclonal
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CD40 Antigens
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Integrin alpha5beta1
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Macrophage-1 Antigen
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Platelet Glycoprotein GPIIb-IIIa Complex
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CD40 Ligand