Activation and regulation of the complement system on injured or stressed endothelium or trophoblasts. Regulation of the feedback loop of the AP on placental trophoblasts occurs through limited proteolytic cleavage of C3b to generate iC3b. This reaction is carried out by a serine protease factor I and the cofactor protein MCP or factor H. Cofactor activity terminates the feedback loop because iC3b does not bind factor B, thereby shutting down the amplification loop. Because SLE and APL syndrome are characterized by autoantibodies that trigger the CP, defective regulation of C4b (a component of the CP C3 convertase) by MCP is also likely to influence the severity of tissue injury and risk for preeclampsia. When tissues are damaged, a delicate balance must be established to allow for repair and recovery. If regulators such as MCP, factor I, or factor H are dysfunctional, excessive complement activation occurs. This may result in placental damage, thrombophilia, and the release of antiangiogenic factors, culminating in preeclampsia. Endothelial cells could be substituted for trophoblasts in this schematic. (Figure provided by Jane Salmon, Hospital for Special Surgery, New York.)