Fibrin depletion decreases inflammation and delays the onset of demyelination in a tumor necrosis factor transgenic mouse model for multiple sclerosis
Autor: | Jan Bauer, Peter Mercado, Katerina Akassoglou, Ryan A. Adams, Hans Lassmann, Sidney Strickland, Vivian Tseveleki, Lesley Probert |
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Jazyk: | angličtina |
Rok vydání: | 2004 |
Předmět: |
Ancrod
Genetically modified mouse anticoagulants Multiple Sclerosis Transgene extracellular matrix Inflammation Mice Transgenic medicine.disease_cause Fibrin Autoimmunity Cell Line Mice Plasminogen Activators medicine Animals ancrod Multidisciplinary biology Tumor Necrosis Factor-alpha Multiple sclerosis autoimmunity Macrophage Activation Biological Sciences medicine.disease Up-Regulation Immunology biology.protein Tumor necrosis factor alpha medicine.symptom medicine.drug Demyelinating Diseases |
Zdroj: | Akassoglou, K; Adams, R A; Bauer, J; Mercado, P; Tseveleki, V; Lassmann, H; et al.(2004). Fibrin depletion decreases inflammation and delays the onset of demyelination in a tumor necrosis factor transgenic mouse model for multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America, 101(17), 6698-6703. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/34d0d512 |
Popis: | In multiple sclerosis, in which brain tissue becomes permeable to blood proteins, extravascular fibrin deposition correlates with sites of inflammatory demyelination and axonal damage. To examine the role of fibrin in neuroinflammatory demyelination, we depleted fibrin in two tumor necrosis factor transgenic mouse models of multiple sclerosis, transgenic lines TgK21 and Tg6074. In a genetic analysis, we crossed TgK21 mice into a fibrin-deficient background. TgK21 fib -/- mice had decreased inflammation and expression of major histocompatibility complex class I antigens, reduced demyelination, and a lengthened lifespan compared with TgK21 mice. In a pharmacologic analysis, fibrin depletion, by using the snake venom ancrod, in Tg6074 mice also delayed the onset of inflammatory demyelination. Overall, these results indicate that fibrin regulates the inflammatory response in neuroinflammatory diseases. Design of therapeutic strategies based on fibrin depletion could potentially benefit the clinical course of demyelinating diseases such as multiple sclerosis. |
Databáze: | OpenAIRE |
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