Biomedical subjects

C J Liang-Takasaki

Publications and source records attributed to C J Liang-Takasaki.

3 recordsLinked to original sources

PubMed1983

Complement activation by polysaccharide of lipopolysaccharide: an important virulence determinant of salmonellae.

Salmonellae with differences only in the O-antigenic polysaccharide of their lipopolysaccharide were previously shown to differentially activate complement via the alternative pathway, causing them to be ingested at different rates by the mouse macrophage-like cell line J774. We now show that this mechanism could explain the different virulence of these strains in vivo. Mouse peritoneal macrophages (thioglycolate induced) ingest these salmonellae at rates that are inversely proportional to the known virulence of the organisms and virtually identical to the rates observed with J774. As with J774, complement is required for this differential uptake, since serum was required and heating (56 degrees C for 30 min) or zymosan treatment of the serum destroyed activity. The known receptor for nonreducing terminal mannose-, fucose-, N-acetylglucosamine, and glucose-containing glyco-proteins did not participate, since uptake was not inhibited by high concentrations of mannan. When clearance of bacteria from the bloodstream of mice was measured, the least virulent organism was cleared very much faster than the most virulent organism, in confirmation of earlier data. When complement in the mice was destroyed by pretreatment with cobra venom factor, the clearance of the least virulent strain was greatly reduced, whereas the very slow clearance of the most virulent strain was unaffected. These data strongly support the hypothesis that when bacteria have polysaccharide in lipopolysaccharide that activates complement efficiently, the bacteria will be phagocytosed, whereas if the polysaccharide activates complement poorly, the bacteria escape ingestion and may cause disease.

Animals↗

PubMed1983

Salmonellae activate complement differentially via the alternative pathway depending on the structure of their lipopolysaccharide O-antigen.

Differences in the O-antigen polysaccharide structure of lipopolysaccharide were previously shown to affect the rate of phagocytosis of Salmonellae strains by the murine macrophage-like cell line J774. Phagocytosis required a serum factor(s) that is labile to heat (56 degrees C for 30 min) and to zymosan treatment, which indirectly suggested the participation of C. We now show, using guinea pig serum, that these bacteria activate C3 at different rates, and this activation is proportional to the later rate of phagocytosis. Activation is predominantly via the alternative pathway, because C4 is not consumed and the reaction proceeds equally well in the serum of C4-deficient guinea pigs. Because the extent of activation of C3 and the subsequent rate of phagocytosis are inversely proportional to virulence, we propose that virulence of a strain may be influenced by the ability of the polysaccharide structure of its lipopolysaccharide to activate the alternative pathway of C, destining it for subsequent phagocytosis.

Animals↗

PubMed1982

Phagocytosis of bacteria by macrophages: changing the carbohydrate of lipopolysaccharide alters interaction with complement and macrophages.

Salmonella transductants and recombinants differing the O-antigenic side chain of their lipopolysaccharide are taken up at different rates by the murine macrophage-like cell line J774. Bacteria containing abequose, mannose, rhamnose, and galactose in O-antigenic side chain were taken up at the slowest rate; the one containing tyvelose instead of abequose was taken up at an intermediate rate; and the one containing mannose, N-acetylglucosamine, and glucose, instead of the above sequence, was taken up at the highest rate. These rates correlate well with the known virulence of these strains; the most virulent is the one taken up slowest, the one taken up at an intermediate rate is less virulent, and the one taken up fastest is the least virulent. The differences in ingestion rates reflect differences in affinity of the bacteria for the macrophages and not in the rate of ingestion once interaction has occurred, suggesting a receptor-mediated process. The majority of uptake is probably dependent on complement, as shown by the requirement for a serum component(s) destroyed by heating at 56 degrees C or by incubation with zymosan. Specific antibody is not required. We therefore postulate that relative virulence in vivo may reflect the relative ability of the polysaccharide of bacterial lipopolysaccharide to activate complement, thus determining the susceptibility of the bacteria to ingestion via the complement receptor of phagocytic cells.

Animals↗