Studies on lysosomes-IX. Localization of bacteriophages and thorotrast and their inflammatory properties

After injection into rabbits, bacteriophages T₂, φX 174, and F₂ became localized to lysosome-rich fractions of liver homogenates. By use of discontinuous sucrose density gradients (1·4-1·8 M) these fractions, rich in arylsulfatase, beta-glucuronidase, and acid phosphatase, could be separated from mitochondrial fractions which were rich in cytochrome oxidase and malate dehydrogenase. Bacteriphages φX 174 and T₂ sedimented together with hydrolase-rich fractions after the phages had been injected in vivo. However, when the phages were admixed with liver homogenates in vitro, they displayed different sedimentation properties. Intraveneous injection of colloidal thorium dioxide (Thorotrast) resulted in the appearance of granules which were rich in acid hydrolases, were denser than the original hydrolase-rich granules, and could be separated from other large granules. When injections of Thorotrast were followed by injections of bacteriophages, the phages became localized not only to the original lysosome-rich fractions of sucrose gradients but also to the densest fractions induced by Thorotrost administration. Therefore, these experiments demonstrated that bacteriophages became localized to lysosomes that had already participated in endocytosis as well as to other lysosomes. Formation of dense granules after injection of Thorotrast was associated with decreases in total hydrolase content of large-granule fractions and increases in beta-glucuronidase activity of unsedimentable fractions and of serum. Isolated hydrolase-rich particles, separated by means of sucrose gradients, were injected into the knee of rabbits, where they induced an acute arthritis with onset 8-10 hr after injection. Appropriate control samples of fractions from gradients poor in acid hydrolases did not induce significant inflammation. Thus, inflammation could be induced in joints by lysosomes which were characterized not only by their content of hydrolases but also by their capacity to participate in endocytosis.