Inhibition of ribonucleic acid synthesis by group A streptococcal pyrogenic exotoxin

Group A streptococcal pyrogenic exotoxins (SPEs) A, B, and C and alpha-amanitin enhance host susceptibility to lethal endotoxin shock. The capacity of SPE C and alpha-amanitin to prepare rabbits for the enhancement phenomenon required pretreatment of the animals 1 to 2 h before giving endotoxin. Endotoxin clearance from the circulation of rabbits pretreated with either SPE C or alpha-amanitin was reduced. Even at the time of death, significant amounts of endotoxin remained in the circulation. It is proposed that the SPE and alpha-amanitin inhibit ribonucleic acid synthesis in Kupffer cells with concomitant alteration in reticuloendothelial clearnace function, allowing endotoxin to persist in the circulation and produce host injury. All three SPE types and alpha-amanitin inhibited ribonucleic acid synthesis by 50% or greater in whole liver cells. Kupffer cells, liver cell nuclei, and liver nuclear extracts; inhibition was observed liver cells from both mice and rabbits. The inhibitory effect by SPEs was dose dependent and was observed after as little as 15 min of preincubation with liver cells. The content of ribonucleic acid in liver nuclei of mice pretreated with either SPE C or alpha-amanitan was reduced, whereas total deoxyribonucleic acid and protein content remained unaltered.