Biocompatibility: complement as mediator of tissue damage and as indicator of incompatibility.

The fully biocompatible surface is the host's own intact endothelium. Blood contact with a damaged or foreign endothelium, or with an artificial surface, will lead to a certain degree of activation of the defense systems. Complement is one of these systems which has a unique property to distinguish between 'self' and 'non-self'. Recent data using complement-specific inhibitors like soluble CR1 and monoclonal antibodies to C5 have shown that complement is not only associated with, but in fact contributes to, the whole body inflammatory reaction seen as a complication to cardiopulmonary bypass (artificial surfaces) and is responsible for the hyperacute rejection of xenografts (foreign endothelium). Complement activation, as measured by assays specific for neoepitopes exposed in the activation products, is a sensitive indicator of bioincompatibility. These assays have been increasingly important after a causal link between complement activation and tissue damage was demonstrated. Efforts have been made to improve the biocompatibility of artificial surfaces, including coating with heparin. This procedure not only improves coagulation compatibility, but also markedly reduces complement activation. Models to study complement compatibility in vitro and in vivo are described, and recommended complement activation assays reviewed.