Biosynthesis in vitro of complement subcomponents C1q, C1s and C1̅ inhibitor by resting and stimulated human monocytes

Abstract

The capacity of cultured human monocytes to synthesize and to secrete the subcomponents of C1 [complement component 1] and C.hivin.1 inhibitor was examined. Non-stimulated monocytes secreted C1q and C1s from day 5 of culture. C1s reached a plateau immediately at its maximum level while C1q secretion increased progressively until the end of the 2nd wk. Between day 12 and day 25, C1q secretion remained nearly constant (1-15 fmol/day per .mu.g DNA, depending on the donor); C1s secretion decreased and even in some cases stopped. C1r and C.hivin.1 inhibitor were not secreted in detectable amounts by these resting cells. Stimulation of monocytes by yeasts, IgG-opsonized sheep red blood cells or latex beads did not modify consistently C1q and C1s secretion. Activation by conditioned media from mitogen-, antigen- or allogeneic-stimulated lymphocyte cultures increased C1q production from 2 to 7 times and reactivated C1s secretion. Under the same conditions of activation, C.hivin.1 inhibitor was secreted (up to 300 fmol/day per .mu.g DNA) and C1r became detectable in culture supernatants. Isolated human monocytes are thus able to synthesize the whole C1 subcomponents; C1, if assembled, could be protected for non-immunological activation by locally produced C.hivin.1 inhibitor. Activated monocytes appear to be a good tool for studying the assembly of C1 subcomponents and the role of C.hivin.1 inhibitor in this process.