Complement-subcomponent-C1̄-inhibitor synthesis by human monocytes

Abstract

By using a radioimmunoassay, C1̄-inhibitor was found to accumulate in the supernatants of human monocyte cultures. The production of this protein was inhibited reversibly by cycloheximide. When C1̄-inhibitor synthesis was compared with C2 synthesis, it was found that C1̄-inhibitor synthesis continued, whereas synthesis of C2 appeared to cease after about 7 days in culture. Immunoprecipitation of supernatants of monocyte cultures that had been pulsed with [35S]methionine showed a specific band with an M(r) of 105,000. Immunoprecipitates of the lysates revealed a band of M(r) 83,000; this was thought to represent a partially or nonglycosylated precursor of C1̄-inhibitor. C1̄-inhibitor produced by the monocytes was shown, by using a haemolytic assay, to be functionally active. However, the functional activity of C1̄-inhibitor was reduced by only 44% in the presence of cycloheximide, whereas the concentration of this protein in cycloheximide-treated culture supernatants fell by more than 93%. This finding suggests that monocytes secrete a second molecule, which inhibits C1̄ activity but is distinct from classical C1̄-inhibitor.