Pathophysiological Consequences of Complement–endothelial Cell Interaction

The complement system is an important component of innate immunity that contributes to the host defence against bacteria] infections and promotes clearance of immune complexes. Components of this system are synthesized by many cell types including hepatocytes and macrophages and are widely distributed both in the circulation and in the extravascular fluids. Complement activation products released in the fluid phase may interact with endothelial cells on the luminal and abluminal sides and activate these cells to express surface proteins (adhesion molecules, tissue factor) and to release molecules (chemokines) involved in the promotion of the inflammatory and coagulation processes as well as in modication of the vascular tone. Another effect of biologically active complement products on endothelial cells is to remove from the cell surface molecules, which, like heparan sulfate, protect from the formation of trombi. Some of the complement components bind to receptors present on the surface of endothelial cells and this is the case of C1q and C5a. Endothelial cells also interact with the terminal complement complex even in the cytolytically inactive form through a mechanism that has not been completely elucidated. The consequences of the complement-dependent activation of endothelial cells vary from a transient and reversible stimulation to a more persistent activation which may lead to endothelial cell and vascular alterations.