Developmentally regulated effects of lipopolysaccharide on biosynthesis of the third component of complement and factor B in human fibroblasts and monocytes

Developmental regulation of the effects of lipopolysaccharide (LPS) on complement protein biosynthesis was studied in human fibroblasts from fetuses, newborn infants and adults, and in human monocytes from newborn infants and adults, using RNA blot analysis and immunoprecipitation of metabolically radiolabelled cell lysates. The responsiveness of the third component of complement (C3) and factor B protein synthesis to LPS is limited by translational mechanisms in the newborn infant and by pretranslational mechanisms in the fetus. Translation of RNA from LPS-induced cells in a rabbit reticulocyte lysate cell-free translating system indicated no differences in specific translational activity between LPS-induced adult and neonatal RNA, suggesting that LPS-induced neonatal C3 and factor B transcripts are translationally competent, but lack either access to relevant protein synthetic pathways or co-factor(s) necessary for translation. Interferon-γ (IFN-γ) enhanced translational activity of LPS-induced C3 and factor B transcripts in neonatal cells, suggesting that lack of translation in these cells may be due to the absence of a necessary co-factor. Experiments with LPS and cycloheximide or LPS and interleukin-1α (IL-1α) suggested that a newly synthesized protein did not participate in translational regulation and that LPS induction did not alter translational activity of IL-1α-induced C3 and factor B transcripts. We conclude that the responsiveness of C3 and factor B protein synthesis to LPS is regulated at developmentally unique and specific steps in gene expression.