Studies on lysosomes. II. The effect of cortisone on the release of acid hydrolases from a large granule fraction of rabbit liver induced by an excess of vitamin A.

Recent studies on the dissolution of cartilage matrix by vitamin A in vivo and in vitro have indicated that the vitamin acts, at least in part, by releasing endogenous acid proteases from cartilage cells (1-5). Dingle (6) found that vitamin A alcohol in vitro liberated acid protease(s) from a particulate fraction of rat liver homogenized in 0.25 M sucrose. This fraction of tissue homogenates contained the bulk of acid hydrolases intimately bound to lysosomes, cytoplasmic organelles described by de Duve (7). Observations from this laboratory, based on earlier experiments by Dingle, suggested that the induction of hypervitaminosis A in vivo caused a similar release of acid protease from lysosomes (8, 9); the action of such enzymes was held responsible for the degradation of protein-polysaccharide complexes in connective tissue. Morphologic expressions of this phenomenon could be seen in rabbit ear and articular cartilage (8) and in the connective tissue (9) of amphibian tails, tentacles, and chondrocranium. These studies, and others carried out at the Strangeways Research Laboratory in Cambridge, England, have also indicated that cortisone and hydrocortisone antagonized the effects of excess vitamin A (10), perhaps by stabilizing the lysosomes of tissues against the vitamin and other injurious agents. Hydrocortisone retarded the release of acid hydrolases from a large granule fraction prepared from rat and rabbit liver after traumatic shock (11) or the injection of bacterial endotoxins (12), and diminished the release effected by mercury arc irradiation (13). It appeared possible, therefore, that