Structural Features and Anti-Complement Activity of an Acidic Polysaccharide from Forsythia suspensa

The complement system can be activated by three separate pathways including the classical pathway (CP), alternative pathway (AP) and lectin pathway (LP) to mobilize defence mechanisms against the invasion of foreign materials such as bacteria and viruses. All three pathways comprise different components and are activated in different fashions but use a common terminal pathway. The CP is activated when C1q interacts with its ligands such as immune-complexes (ICs), the LP is activated when MBL or ficolins binds to certain carbohydrates and the AP can be activated by spontaneous C3 hydrolysis or via properdin, thereby generating C3 (H2O) which can bind factor B (fB). Activation of each of these pathways generates C3- convertases resulting in activation of the common terminal pathway and generating several effector processes, such as chemotaxis by C3a and C5a, opsonization by C3b, and lysis by the membrane attack complex. Excessive or uncontrolled activation of the complement system might lead tosevere complement-mediated disorders, such as Alzheimer’s disease, Pick’sdisease and Myasthenia gravis (MG). A large number of anti-complement therapeutic agents have been developed and some have been found to be beneficial in reducing tissue injury in a number of animal models of severe complementdependent inflammation.

Numerous natural or semi-synthetic polyanions, such as complestatin, derivatized dextrans, chondroitin sulfate, dextran sulfate and heparin have been found to inhibitcomplement activation. However, many of these compounds are toxic and most of them require relatively high concentrations for inhibiting complement activation both in vitro and in vivo.