Pharmaceutical Manipulations of the Complement Cascade

The complement system constitutes an integral component of both host defense against infections and of the inflammatory process. The activities involved in both processes are derived from plasma proteolytic fragments of inert precursor proteins and from the fusion of multiple protein molecules. Together with the twenty or more plasma proteins that comprise the complement system, a number of distinct cell surface complement receptors have been recognized, which exhibit defined ligand specificity. These receptors are expressed on cells involved in the inflammatory process and on cells of the immune system. This information has been derived from the biochemical investigation of the proteins that constitute the complement system, their reaction products, and cellular receptors. The significance of these observations has been provided by the study of the clinical consequences of genetic deficiences of complement proteins and receptors in humans and the exploration of experimental disease models.