Pathophysiology of the Interaction between Complement and Non-Complement Proteases

Abstract

The complement system is a group of plasma proteins that can interact with antigen antibody complexes and the surface of microbes and certain cells for the purpose of protecting the host against such noxious antigens (1–3). The complement proteins account for about 5% of the total plasma proteins; activation of the complement proteins occurs sequentially and is characterized by a conversion of proteolytic zymogens to active proteinases that catalyze conversion of other zymogens to active enzymes further down the sequence (4). There are two pathways of activation for complement, the classical pathway that is generally dependent on the formation of specific antibody, and the alternative pathway, that represents a system for resistance to infection in a non-immune host. One should note that of the twenty complement components, only five are so far identified as proteinases as shown in the activation scheme on Fig. 1: The proteinases are C1¯r, C1¯s, C2¯a in the classical pathway and D¯ and Bb¯ in the alternative pathway; there is no zymogen form for D¯. All are serine proteases whereby C1¯r, C1¯s and D¯ possess catalytic peptide chains of about 25’000 m wt. Trypsin, plasmin, pronase and chymotrypsin are known to activate C1¯ (2); accordingly tryptic and chymotriptic inhibitors, as well as liquoid and antrypol can be used to inhibit C1¯s (8), whereby a naturally occuring plasma protein, the C1 esterase inhibitor inhibits C1¯r and C1¯s but also plasma kallikrein, plasmin, trypsin, chymotrypsin, Hagemann factor (factor XIIa) and activated thromboplastin antecedent (XIa).