Chloroquine treatment does not cause phospholipid storage by depleting rat liver lysosomes of acid phospholipase A.

Chronic treatment of rats with chloroquine causes phospholipid storage in the lysosomes of liver and other tissues. This could be due to chloroquine-induced depletion of liver lysosomal phospholipase A. Alternatively, it could be caused by chloroquine inhibition of intralysosomal phospholipid catabolism. We treated rats with chloroquine in a dosage schedule sufficient to cause a 35% increase in liver phospholipid content. Acid phospholipase A activity was increased in liver homogenates and in lysosomal preparations obtained from chloroquine-treated animals. Thus, while fibroblasts respond to chloroquine treatment by cellular depletion of certain acid hydrolases as shown by others, the levels of acid phospholipase A increase in liver. Our results provide additional new support for the hypothesis that inhibition of lysosomal phospholipase A activity is the major mechanism of chloroquine-induced phospholipidosis.