Pseudomonas aeruginosa exotoxin in mice: localization and effect on protein synthesis

We studied the fate of (125)I-labeled Pseudomonas aeruginosa (PA 103) exotoxin injected intravenously into mice and the effect of the exotoxin on the protein synthesis of various organs. After 2 h, only 5% of the injected label remained in the blood, in comparison with 30% of the injected control, consisting of [(125)I]bovine serum albumin. The highest concentration of radioactivity was consistently observed in the kidneys of toxin-treated mice. Lesser amounts of the label were found in the liver and the spleen. The heart, pancreas, lung, and brain showed very little uptake. Approximately 30% of the label (non-trichloroacetic acid precipitable) was recovered from the urine within 2 h after the injection. The behavior of [(125)I]toxoid was similar to that of the [(125)I]toxin. In contrast, in [(125)I]bovine serum albumin-treated mice, the label was uniformly distributed among the organs examined, and the concentration was low. After intravenous administration of the exotoxin, a 50% inhibition of protein synthesis was observed in the liver within 4 h, and virtually complete inhibition was observed shortly before the time of death. Kidney and spleen displayed slight reduction of protein synthesis at 2 to 4 h and approximately 50% reduction during the terminal stage. It appeared that the highest concentration of the toxin occurred in the kidney, where it was degraded, but its greatest toxic effect took place in the liver.