The intracellular distribution of cathepsins and other acid hydrolases in mouse peritoneal macrophages

Abstract

Acid hydrolases, among them cathepsins A, B, C, and D, and their intracellular distribution have been studied in mouse peritoneal macrophages, a model commonly used for the study of mononuclear phagocyte functions in host-parasite relationships and in the immune response. Thioglycollate stimulated peritoneal macrophages showed high specific activities of acid hydrolases in compatison to liver and spleen. Fractionation of these macrophages by differential and isopycnic sucrose density centrifugation showed heterogeneous enyzme distribution patterns which were different for the various hydrolases studied. Thus, these enzymes appeared to be associated with particles of varying weight and density and in the different particles the ratios of the various acid hydrolase activities were quite dissimilar. With the majority of hydrolases a portion of the enzyme activity was found in fragile heavy particles of densities higher than 1.25 that sedimented together with the nuclei. Cultured macrophages derived from the non-irrated peritoneum exhibited a less heterogenous distribution pattern for acid phosphatase than did the thioglycollate stimulated cells. The heterogeneity of acid hydrolase distributions in the thioglycollate induced macrophages was attributed to their physiologic state of stimulated endocytosis causing a continuous formation of primary and secondary lysomes. Under certain conditions macrophages might contain lysosome-like particles with cathepsin ratios unfavorable for complete proteolysis. The existence of such particles is suggested as a possible explanation for the persistence of immunogenic protein within these cells.