New Aspects in Thrombotic Research: Complement Induced Switch in Mast Cells from a Profibrinolytic to a Prothrombotic Phenotype
Pathophysiology of Haemostasis and Thrombosis
Mast cells, strategically located in the vicinity of blood vessels, are multifunctional effector cells participating in the modulation of various inflammatory and cardiovascular disease processes by actively releasing a wide variety of vasoactive mediators. These cells have also been implicated in the regulation of thrombosis and the development and progression of atherosclerosis. By expressing enzymatically active tissue typeplasminogen activator (t-PA), human mast cells (MC) might play a role
... in endogenous fibrinolysis and extracellular matrix remodelling -both processes that are essential in the pathogenesis of cardiovascular disorders. However, when treated with the anaphylotoxin C5a, mast cells express the PA inhibitor 1 (PAI-1) in excess over t-PA. In context with studies suggesting a role for mast cells and components of the complement system in the development of cardiovascular disease our results lead to the hypothesis that mast cells by producing t-PA in a resting state and by expressing PAI-1 when activated by C5a might participate in the modulation of the balance between proteases and pro-tease inhibitors regulating tissue injury and repair in these disease processes. In addition, C5a might upregulate PAI-1 in mast cells to prevent its own inactivation by plasmin in an autocrine or paracrine fashion.