Studies on lysosomes. I. The effects of endotoxin, endotoxin tolerance, and cortisone on the release of acid hydrolases from a granular fraction of rabbit liver.

Granular fractions sedimenting between 800 g and 15,000 g have been prepared in 0.25 M sucrose from the livers of normal young rabbits and from the livers of rabbits injected with A. aerogenes endotoxin. As early as 5 minutes after endotoxin, there was an augmented release of two enzymes, beta glucuronidase and cathepsin, into the supernatant of fractions which had been incubated or incubated and irradiated with a mercury vapor lamp at 37 degrees C. These effects were maximum at 30 minutes after endotoxin and were associated with a depletion of the total activities of the two enzymes within the granules. Concurrently there was a rise in the activity of the two enzymes in fractions of the homogenate which were unsedimentable at 15,000 g. Fractions prepared from animals made tolerant to endotoxin no longer responded to incubation and irradiation by an augmented release of these two hydrolases, nor did fractions prepared from animals pretreated with glucocorticoids. Pretreatment with DOCA did not prevent release of enzymes after endotoxin. The results have been interpreted to indicate that one consequence of the injection of endotoxin is an effect upon the stability of lysosomes, with subsequent release of acid hydrolases into the cell sap or surrounding tissue. Glucocorticoids may exert their pharmacologic effects through the protection of these subcellular particles against a variety of injurious agents.