Investigations on the mechanism of stimulation of non-specific immunity by bacterial lipopolysaccharides

Abstract

The stimulation of non-specific immunity by lipopolysaccharides could not be correlated with the serum properdin level at the time of challenge. Zymosan was effective in stimulating an increase in properdin without raising resistance to infection. The development of a low properdin level during Esch. coli infection did not inevitably lead to death.

The fate of ³²P-labelled lipopolysaccharide (³²P-LP) after intravenous injection was followed in mice and guinea pigs. Most of it was accumulated rapidly in the reticulo-endothelial system. About a third was removed from the blood more slowly than the remainder, probably owing to a smaller particle size. Some of the ³²P was excreted in the urine as inorganic phosphate. Very little radioactivity was found in the circulating leukocytes.

The blood clearance of ³²P-LP was slowed by the administration of nonradioactive lipopolysaccharide 30 min. previously. When this interval was 48 hr. the reticulo-endothelial system was found to be hyperactive in terms of rate of clearance and phagocytic capacity. This was accompanied by an increase in the number of active macrophages in the liver and, to a lesser extent, in the spleen. These biphasic changes in the phagocytic activity of the R.E.S. parallel the decreased and increased resistance to infection following the injection of microgram amounts of lipopolysaccharide.

Successive depression and stimulation of the R.E.S. also followed the injection of milligram amounts of Thorotrast. The hyperactive phase was accompanied by increased resistance to Esch. coli infection and decreased resistance to Salm. typhimurium infection.

The lipid A component of lipopolysaccharide was also taken up by the R.E.S. which it stimulated. Resistance to both Esch. coli and Salm. typhimurium infections was enhanced.

The basis of lipopolysaccharide-induced non-specific immunity is discussed in relation to changes in the properdin and reticulo-endothelial systems. The superiority of lipopolysaccharide over other colloids in stimulating immunity is considered to be determined by lipid A.