C1 INHIBITOR - DIFFERENT MECHANISMS OF REACTION WITH COMPLEMENT COMPONENT C1 AND C1S

Inactivation of human complement subcomponent C1BARs by its regulator C1 inhibitor at physiological ionic strength proceeded at a 3-fold higher rate when C1BARs was in the physiological C1BAR complex with subcomponents C1q and C1BARr rather than as a purified subunit. When the C1BAR complex was disassembled by chelation of calcium, the C1BARs 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 C1BARs with C1 inhibitor but greatly diminished the rate of reaction of intact C1BAR. Addition of heparin accelerated the inactivation of purified C1BARs by C1 inhibitor up to 25-fold but increased the inactivation of intact C1BAR only about 5-fold. These differences in the inactivation of C1BARs by C1 inhibitor, depending on whether the proteinase is free or complexed with other subcomponents of C1BAR, suggest different mechanisms of reaction. Occurrence of subcomponent C1BARs in a macromolecular complex with C1q and C1BARr, thus, appears to be critical not only for directing its physiological activation but also its inactivation.