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 and C1 inhibitor was examined. Non-stimulated monocytes secreted C1q and C1s from day 5 of culture. C1s reached a plateau immediately at its maximum level, whereas C1q secretion increased progressively until the end of the second week. Between day 12 and day 25, C1q secretion remained nearly constant (1-15 fmol/day per microgram of DNA, depending on the donor), whereas C1s secretion decreased and even in some cases stopped. C1r and C1 inhibitor were not secreted in detectable amounts by these resting cells. Stimulation of monocytes by yeasts, immunoglobulin G-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 re-activated C1s secretion. Under the same conditions of activation, C1 inhibitor was secreted (up to 300 fmol/day per microgram of 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 from non-immunological activation by locally produced C1 inhibitor. Activated monocytes appear to be a good tool for studying the assembly of C1 subcomponents and the role of C1 inhibitor in this process.

An Alternative Role of C1q in Cell Migration and Tissue Remodeling: Contribution to Trophoblast Invasion and Placental Development

“…Staining for C1q was also observed in the villi, particularly in the Hofbauer cells that displayed a strong signal. This is not surprising because they belong to the monocyte/ macrophage lineage known to be a major source of C1q (49)(50)(51). A low level of staining was also apparent in villous trophoblast cells, most likely due to C1q deposits from maternal blood, as these cells were found to lack the C1qC message required for the assembly of C1q.…”

Neutrophils Induce Astroglial Differentiation and Migration of Human Neural Stem Cells via C1q and C3a Synthesis

“…However, C1q can be synthesized in the absence of C1r and C1s by a variety of cell types, including PMN (47,70,71). Furthermore, a large body of evidence has shown upregulation of C1q in the CNS following injury/disease/aging (72)(73)(74), suggesting that C1q alone may have nontraditional functions (75,76).…”

Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium

“…One possible explanation for the different distribution of C1q on ECs from various districts is that C1q is constitutively expressed on the surface of DECs. ECs are not listed among the C1q-producing cells that include primarily macrophages (Bensa et al, 1983), fibroblasts (Skok et al, 1981), epithelial cells of the intestinal and urogenital tracts (Bing et al, 1975), follicular dendritic cells and interdigitating cells (Schwaeble et al, 1995). The finding that HUVECs, UtMECs and ADMECs express only one or two of the mRNAs were incubated with mAb 74.5.2 or mAb 60.11, both directed to gC1q-R, or rabbit anti-human cC1q-R antibodies.…”