Impaired Detoxification as a Mechanism of Lead Acetate-Induced Hypersensitivity to Endotoxin

Abstract

Actinomycin D was employed to profoundly enhance the sensitivity of mice to endotoxin in order to bioassay submicrogram amounts of endotoxin. Homogenates of rat liver and spleen were able to detoxify endotoxin as bioassayed in actinomyein-treated mice. Lung, kidney, heart, and brain homogenate did not possess the ability to significantly detoxify endotoxin. Lead acetate, which profoundly sensitizes rats to endotoxin, enhanced the vascular clearance of colloidal carbon and also reduced detoxification of endotoxin by liver and spleen homogenates. Enhanced phagocytosis, resulting in accumulation of endotoxin in macrophages, coupled with the failure in endotoxin inactivation or detoxification, appears to be the mechanism of lead acetate-induced endotoxin hypersensitivity.