C1 inhibitor: different mechanisms of reaction with complement component C1 and C1s.
Inactivation of human complement subcomponent C1-s by its regulator C1 inhibitor at physiological ionic strength proceeded at a 3-fold higher rate when C1-s was in the physiological C1- complex with subcomponents C1q and C1-r rather than as purified subunit. When the C1- complex was disassembled by chelation of calcium, the C1-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 C1-s with C1 inhibitor but greatly diminished the rate of reaction of intact C1-. Addition of heparin accelerated the inactivation of purified C1-s by C1 inhibitor up to 25-fold but increased the inactivation of intact C1- only about 5-fold. These differences in the inactivation of C1-s by C1 inhibitor, depending on whether the proteinase is free or complexed with other subcomponents of C1-, suggest different mechanisms of reaction. Occurrence of subcomponent C1-s in a macromolecular complex with C1q and C1-r, thus, appears to be critical not only for directing its physiological activation but also its inactivation.
Hortin
G L
GL
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
Trimpe
B L
BL
D003172:Complement C1 / Q000378:metabolism*; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D003173:Complement C1s / Q000378:metabolism*; D006801:Humans; D007700:Kinetics
D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D003173:Complement C1s