Biosynthesis of C4 by mouse peritoneal macrophages. II. Comparison of C4 synthesis by resident and elicited cell populations.

Five elicited macrophage populations synthesized one-third to one-tenth as much hemolytically active C4 when compared with resident peritoneal macrophages. This decrease in functional C4 activity was not caused by inhibitors or protease activity in the elicited macrophage supernatants. Analysis of C4 antigen indicated a similar reduction in the elicited cells compared with the resident macrophages. A defect in precursor processing or secretion was deemed unlikely because the intracellular C4 precursor was appropriately reduced in the elicited cells. We postulate that mouse resident peritoneal macrophages are a pluripotent cell population with broad capabilities in regard to the initiation of the inflammatory response. In contrast, elicited or activated macrophages may be more specialized cells, with one manifestation of this being the "down" regulation of C4 synthesis.

Biosynthesis of C4 by mouse peritoneal macrophages. I. Characterization of an in vitro culture system and comparison of C4 synthesis by "low" vs "high" C4 strains.

C4 biosynthesis and secretion in mouse resident peritoneal macrophage cultures was examined by functional and antigenic analysis. The rate of secretion of functional and antigenic C4 decreased in parallel in short-term culture despite constant total protein secretion and increasing factor B secretion. Feedback inhibition and protease degradation did not account for the decreasing rate of C4 secretion. Despite a 10-fold difference in plasma C4 levels between high C4 (H-2d haplotype) and low C4 (H-2k haplotype) mouse strains, resident peritoneal macrophages from both strains synthesized and secreted similar amounts of antigenic and functional C4 in short-term culture. The C4 secreted by H-2d and H-2k macrophages was relatively stable, because it exhibited only approximately 2% loss of hemolytic activity per hour in culture. These data suggest that an unidentified environmental signal leads to the specific decrease in C4 synthesis and secretion by peritoneal macrophages and that a regulatory defect may not be present, at least in macrophages, to account for the low C4 levels in the H-2k haplotype.

Mutants of Salmonella typhimurium that are insensitive to catabolite repression of proline degradation.

In Salmonella typhimurium the two enzymes of proline catabolism, proline oxidase and Delta(1)-pyrroline-5-carboxylic acid dehydrogenase, are subject to catabolite repression when the cells are grown in the presence of glucose. Mutants partially relieved of catabolite repression (PutR) for the proline catabolic enzymes have been isolated by selection on agar plates containing glucose and proline. The specificity of the catabolite repression-insensitive character for the enzymes of proline utilization has been confirmed by an analysis of other unrelated catabolic enzymes. Histidase and amylomaltase of the mutant strains are equally as sensitive to glucose repression as are the enzymes from the wild type. All four PutR mutants exhibit higher induced and higher basal levels of proline oxidase as compared with the corresponding wild-type levels. The mutations of three strains tested are cotransducible with constitutive, pleiotrophic-negative and structural gene mutations of the put region. Three-factor crosses indicate that two putR mutations are located at one end of the cluster of put mutations.