CI Inhibitor: Different Mechanisms of Reaction with Complement Component Ci¯t and Ci¯ts

Abstract

Inactivation of human complement subcomponent Cl¯s by its regulator C1 inhibitor at physiological ionic strength proceeded at a 3-fold higher rate when Cl¯s was in the physiological CT complex with subcomponents C1q and Cl¯r rather than as a purified subunit. When the Cl¯ complex was disassembled by chelation of calcium, the Cl¯s subcomponent was inactivated by C1 inhibitor at rates similar to those for the purified proteinase. Increasing ionic strength had little effect on the reaction of purified Cl¯s with C1 inhibitor but greatly diminished the rate of reaction of intact CT. Addition of heparin accelerated the inactivation of purified Cl¯s by Cl¯ inhibitor up to 25-fold but increased the inactivation of intact Cl¯ only about 5-fold. These differences in the inactivation of Cl¯s by Cl¯ inhibitor, depending on whether the proteinase is free or complexed with other subcomponents of Cl¯, suggest different mechanisms of reaction. Occurrence of subcomponent Cl¯s in a macromolecular complex with Cl¯q and Cl¯r, thus, appears to be critical not only for directing its physiological activation but also its inactivation.