title: Regulation of Classical Pathway of Complement Activation by Interferons.
abstract: Though complement activation in normal physiological conditions is under regulation of special proteins relevant to complement system, there is a number of other humoral factors, which may also act as activators or inhibitors of complement activation due to significant increase in their concentration during inflammation. Administration of interferons in rheumatic patients leads to pronounced changes in immune response including complement system. It is very likely that interferons may be regulators of complement activation. In this connection, influence of recombinant alpha2b- and gamma-interferon on C5-convertase formation was investigated. We have obtained stabilized and bound on sheep erythrocyte membrane C3-convertase with prolonged period of half-inactivation and ability of transformation into C5-convertase in the presence of employed interferons. Addition of interferons to the model system caused inhibition of complement activation and abrogation of complement-induced hemolysis. Inhibition constants were found to be 133000 and 170000 IU/ml for alpha2b- and gamma-interferon, respectively. Despite, these values are higher than natural serum interferon concentrations, it is possible that under inflammation local synthesis of interferons may by performed by attracted leukocytes. In this case it seems difficult to define concentration of interferons as well as revealed by us interferon inhibition of complement activation in situ. This inhibition has not been previously described and represents a new mechanism of interferon action. Binding of activated C3b complement component to interferons is probably of great physiological importance leading to constraint of complement cascade activation as well as to inactivation of excessive interferon quantity.
authors.affiliation: Institute of Rheumatology of RAMS, Moscow, Russia.
authors.forename: T. V.
authors.initials: TV
authors.lastname: Lebedeva
authors.forename: L. V.
authors.initials: LV
authors.lastname: Kozlov