Chapter 31 - Role of Mast Cells in Endogenous Fibrinolysis and Related (Patho)physiological Processes

Abstract

This chapter discusses the contribution of mast cells (MC) to endogenous fibrinolysis as part of the tissue repair following inflammatory or other local reactions accompanied by (transient) fibrin deposition. The concept is based on the observation that MC, in addition to heparin and other mediators and molecules, express enzymatically active tissue-type plasminogen activator (tPA) and urinary-type plasminogen activator (uPA) receptor (uPAR), but do not express inhibitors of tPA or uPA. Following an IgE-dependent (or independent) activation of MC, the release of vasoactive mediators leads to an increase in capillary permeability. The increased vascular permeability leads to the translocation of plasma molecules and blood cells into the tissues, and the extravasation of fibrinogen is followed by the formation of fibrin. The cellular basis of endogenous fibrinolysis has been a matter of numerous speculations. Endothelial cells (EC) apparently are a source of both tPA and uPA. Activated macrophages and smooth muscle cells are also capable of producing plasminogen activators. The profibrinolytic activities of tPA and uPA are counterbalanced by plasminogen activator inhibitors. The possible role of SCF and c-kit in the repair functions of MC is the subject of ongoing research. One important aspect is that stem cell factor (SCF) is detectable in activated (isolated) EC as well as in local sites of thrombosis. The emerging concept is that the same cell that activates EC and induces a significant capillary leak or prothrombotic condition in the (micro-) vasculature, also contributes to local fibrinolysis as part of specific repair.