The Complex Roles of Anaphylatoxins in Allergic Asthma and Autoimmune Diseases

Complement has a long-recognized role as a lytic effector system that protects against microbial pathogens as well as a mediator of acute and chronic inflammatory responses. Many of the inflammatory properties related to complement activation can be related to the complement cleavage fragments C3a and C5a, the so-called anaphylatoxins. Cloning and subsequent gene targeting of their corresponding receptors, as well as generation of specific C3a and CSa inhibitors, have fueled new interest in studies aimed at defining the roles of the anaphylatoxins in inflammatory diseases. Traditionally, the anaphylatoxins have been considered mediators of end-stage effector mechanisms. However, recent data from animal models of allergic asthma suggest that C3a and C5a provide a critical link between innate and adaptive immunity. Further, the anaphylatoxins appear to form a sophisticated regulatory network together with immunoglobulin G Fc receptors that links regulatory events with effector activities in autoimmune disease. In this review, we will focus exclusively on the role of C3a and C5a in allergic asthma and autoimmune disease.