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

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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.