Effect of endotoxin on rat liver. Analysis of acid phosphatase isozymes in the liver of normal and endotoxin-treated rats.

Lysosomal enzymes in parenchymal and sinusoidal cells in rat liver were sequentially studied following administration of endotoxin and correlated with fine structural changes in liver cells. In normal rat liver, there are three types of acid phosphatase isozymes, two present only in parenchymal cells and the other specifically in sinusoidal cells. The parenchymal acid phosphatase isozymes hydrolyze preferentially AMP and CMP, while the sinusoidal isozyme hydrolyzes phenylphosphate. After an intraperitoneal injection of an LD50 dose of endotoxin, the activity of the sinusoidal acid phosphatase isozyme reached a maximum at 1 hour, and was followed by an elevation of the activity of the isozymes derived from parenchymal cells. Within 1 hour after the injection, morphologic changes were most prominent within sinusoids, including swelling of the Kupffer cells and accumulation of polymorphonuclear leukocytes, platelets, and fibrin clumps on and around the Kupffer cells. Degenerative changes in parenchymal cells were observed following the initial reactions within sinusoids. The results of the present study are compatible with the hypothesis that the hepatic parenchymal cell damage induced by endotoxin is mediated by the initial changes within sinusoids, rather than by the direct aciton of endotoxin on the parenchymal cells.