Pseudomonas aeruginosa exotoxin in mice: loca1ization and effect on protein synthesis

The histopathology and serum enzyme levels of mice inoculated intravenously with Pseudomonas aeruginosa exotoxin were studied. The toxin exerted a marked effect on the liver but elicited no demonstrable microscopic changes in other organs. The microscopic lesions caused in the liver by a single injection of two 50 % lethal doses (LD50) of toxin (2.3 ~g) were characterized by necrosis, cellular swelling, and fatty change within 4-8 hr and near total hepatocellular necrosis at 48 hr. Hepatic necrosis was accompanied by a parallel rise in serum levels of aspartate and alanine aminotransferases and alkaline phosphatase. A single injection of 10 LD50 elicited similar but somewhat more rapid degeneration. No progressive lesions were seen after injection of toxoid or of 0.5 LD50 of toxin. Our previous study [1] demonstrated that the exotoxin of Pseudomonas aeruginosa [2, 3] causes an early and rapidly increasing reduction in pro-tein synthesis in the liver of the mouse. After iv injection o ~ the toxin, protein synthesis was in-hibited by 50 % within 2-4 hr, and inhibition was virtually complete before death. Although a re-duction in protein synthesis was noted in other organs, it occurred considerably later and to a Received for publication May 19, 1975, and in revised form September 22, 1975. This investigation was supported by projects no. M4319.01.0009BGGY and M4318.01.0006AGG6 from the Naval Medical Research and Development Command, Department of the Navy. The animals used in this study were handled in ac-cordance with the provisions of Public Law 89-44 a