Novel aspects and new roles for the serine protease plasmin.
The serine protease plasmin is distributed throughout the human body in the form of the zymogen plasminogen. The plasminogen activation system is mostly recognized for its fibrinolytic activity but is also upregulated in chronic inflammatory diseases, including atherosclerosis and arthritis. Plasmin can bind to a variety of cells, including monocytes, through low-affinity binding sites and triggers aggregation of neutrophils, platelet degranulation and arachidonate release from endothelial cells. In monocytes, plasmin elicits full-scale proinflammatory activation, including lipid mediator release, chemotaxis and cytokine expression, as well as induction of other proinflammatory genes. The effects of plasmin are specific, require the active catalytic center and can be antagonized by lysine analogues, implying binding of the plasmin molecule to the cell membrane through its lysine binding sites. In view of the upregulation of the fibrinolytic genes in chronic inflammatory diseases, cell activation by plasmin is likely to play a major pathophysiological role, a view that is further supported by data from transgenic mice.
Syrovets
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Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Helmholtzstr. 20, 89081 Ulm, Germany.
Simmet
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D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D004789:Enzyme Activation; D005341:Fibrinolysin / Q000235:genetics / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D050356:Lipid Metabolism; D009000:Monocytes / Q000276:immunology / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
D005343:Fibrinolytic Agents; D010958:Plasminogen; D005341:Fibrinolysin