Biosynthesis of the third component of complement (C3) in vitro by monocytes from both normal and homozygous C3-deficient humans.

Abstract

A B S T R A C T Human monocytes synthesized the third component of complement (C3) up to 5 wk in vitro. Evidence for net C3 synthesis was based on (a) incorporation of 14C-labeled amino acids into C3 protein, (b) identity of the allotype of C3 produced in vitro with that of the doner's serum C3, even in the presence of carrier C3 protein of a different allotype; (c) correspondence of electrophoretic mobility, size, and subunit structure of C3 protein produced in vitro with serum C3; (d) inhibition of C3 production with cycloheximide.Monocytes from two unrelated C3-deficient patients were studied under conditions that supported C3 synthesis by normal monocytes. Serum from each of the patients contained <1% of the normal C3 concentration, but their monocytes produced C3 at -25% of the normal rate when studied after 2 wk in vitro. The C3 produced in vitro by monocytes from one of the patients had the molecular weight of normal serum C3 and dissociated appropriately under reducing conditions. Monocytes from C3-deficient patients could not be distinguished from normals on the basis of morphology, rosetting with C3-coated erythrocytes, or rates of C2, and total protein synthesis.

A new role for complement C3: Regulation of antigen processing through an inhibitory activity

“…Increasing evidence from in vivo as well as in vitro experiments has raised since, Bottger et al, 1986Ochs et al, 1983Pepys, 1974 Page / 2 11 ) and ii) they are known to secrete larger amount of C3 at sites of inflammation than other APC ( ). Our et al, Einstein et al, 1977 results constitute the first evidence that C3b can indeed inhibit lysosomal proteases. This inhibitory activity is specific of C3b and is supported by the C3c fragment.…”

A C3(H20) recycling pathway is a component of the intracellular complement system

“…In agreement with this, we demonstrated C3 mRNA in the cell lines examined (Supplemental Figure 6). Although most C3 is secreted, it has been shown that some cell types store C3, such as human neutrophils (36) and monocytes (37). The derivation and composition of these C3 stores have not been delineated.…”

Production of complement components by cells of the immune system

“…Additionally, C2 and C4, which are also part of the CP, have been shown to be secreted by monocytes [26,28,[57][58][59]. Monocytes also secrete various AP components as C3, FB, FD and FP [24,[59][60][61][62][63][64]. Moreover, the terminal pathway components C5, C6, C7, C8 and C9 are secreted, which are able to assemble as MAC [24,65].…”