Allograft rejection: effect of local synthesis of complement

The complement system is known for its ability to participate in non-specific inflammation and membrane injury as well as contributing to antigen-specific immune stimulation. In renal transplantation, the complement cascade behaves true to form in that both non-immune- and immune-mediated destruction of the renal tubules are complement dependent. What is remarkable, however, is the extent of involvement of local synthesis of complement in both of these injuries, suggesting that the extravascular tissue compartment is the domain of local synthesis, whereas the effect of circulating complement is much less. This creates a new paradigm for studying the influence of local synthesis of complement in other organ-based diseases and underlines the need for tissue-targeting strategies in successful therapeutic development.