LPS isolated from the outer membrane of gram negative bacteria has been shown to increase specifically the production of C3 by human blood monocytes. The availability of cDNA probes for C3 as well as C2 and factor B and structurally altered LPS permitted examination of the biosynthetic regulation of and structural requirement for this effect of LPS. Poly-A RNA was isolated from monocytes incubated in the presence and absence of LPS and subjected to Northern blot analysis using single strand (M13) cDNA probes. C3 mRNA increased from 5 to 10 fold without a comparable increase in C2 or factor B mRNA. To determine the structurally relevant portions of the LPS molecule, monocyte monolayers were incubated in the presence of lipid A inactivated (by alkaline hydrolysis) LPS, LPS isolated from a polysaccharide deficient mutant of S. minnesota, lipid X, and a monoacylgluco-samine-l-phosphate derivative of lipid X. using biosynthetic labelling with 35S methionine, immunoprecipitation, and EDS-PAGE, polysaccharide deficient LPS and lipid X increased newly synthesized C3, but lipid A inactivated LPS and the lipid X derivative did not. These data suggest that LPS increases C3 synthesis by human monocytes pretranslationally and that the reducing end subunit of the lipid A portion of the molecule is the minimal structural requirement for this activity.
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Strunk, R., Cole, F. 1030 PRETRANSLATIONAL REGULATION OF THE SYNTHESIS OF THE THIRD COMPONENT OF COMPLEMENT (C3) IN HUMAN BLOOD MONOCYTES BY THE LIPID A PORTION OF LIPOPOLYSACCHARIDE (LPS). Pediatr Res 19, 282 (1985). https://doi.org/10.1203/00006450-198504000-01060