Properdin and Complement Activation: A Fresh Perspective

The C3 convertases are the major proteases of the complement cascade and are assembled at the site of complement activation via several different pathways. Properdin's functional role in stabilizing the alternative pathway convertase has been long established; however, new evidence demonstrates that properdin can also bind to certain microbial surfaces, and provide a platform for de novo convertase assembly. Therefore, properdin participates in two distinct mechanisms for complement activation: the alternative pathway and a properdin-directed pathway. Previous work had implicated the alternative pathway in the initiation and/or progression of several autoimmune diseases and in the host defense against certain bacterial pathogens. Those conclusions were based on evidence that cannot distinguish effects of the alternative pathway from effects of the properdin-directed pathway. With the identification of the new role for properdin in C3 convertase assembly there became a pressing need to reassess the mechanisms of complement activation, determine the specific role of properdin in each of these pathways, and explore the new therapeutic avenues that could arise.