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 Printable version |
Plasminogen activation and leukocyte pericellular proteolysis |
Hématologie. Volume 2, Number 5, 377-86, Septembre - Octobre 1996, REVUES ET MINI-REVUES
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 Résumé
Article gratuit
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Author(s) : Edouardo Anglés-Cano |
Summary : Limited pericellular proteolysis produced by leukocytes in response to tissue and/or vascular injury plays a major role in extracellular matrix degradation, lysis of fibrin, activation of growth factors, and removal of tissue debris. Several serine proteinases including plasminogen activators, neutrophil elastase, proteinase 3 and cathespin G, as well as some metalloproteinases (Type I and type IV collagenases) have been implicated in these proteolytic reactions. These enzymes are stored in specific cellular compartments and are secreted by leukocytes in response to inflammatory mediators. The extent of the proteolytic response is modulated by factors including the rate of secretion of enzymes, and the rate of activation of pro-enzymes such as latent collagenases. Interactions of these enzymes with either cellular receptors, membrane proteins, cofactors or insoluble substrates ensure focalisation of these reactions, optimal catalytic constants and protection from inhibitors present in the soluble phase. Thus, pro-urokinase bound to its cellular receptor cleaves efficiently plasminogen bound to membrane proteins and the resulting membrane-bound plasmin degrades matrix proteins, and activates latent growth factors and pro-enzymes. Besides its known role as a mediator of a pericellular proteolysis, the urokinase receptor may also participate in cell adhesion, signal transduction and cell chemiotaxix. This receptor is deficient on peripheral blood leukocytes in patients with paroxysmal nocturnal haemoglobinuria and acquired clonal defect in bone marrow-derived cells, clinically associated with intravascular hemolysis, hemoglobinuria and an increased frequency of venous thrombosis probably related to deficient plasminogen activation. Neutrophil elastase and cathepsin G are also localised on the cell membrane through interaction with cationic proteins. Cell-surface binding of enzymes constitutes, therefore, a major advantage, as proteinase inhibitors present in the extracellular milieu cannot inhibit cell-surface bound actif enzymes ; their proteolytic activity is thus confined to the pericellular environment. Other mechanisms such as the oxidative inactivation of inhibitors or the tight binding of metalloproteinases to their insoluble substrates, may contribute to the intensity of the proteolytic response. However, dysregulation of these processes leading to an excessive or inappropriate proteolytic activity may play a pivotal role in some pathological processes. |
Keywords : pericellular proteolysis, plasminogen activation, leukocytes. |
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