RES History

Join Communication Committee member Samson Kosemani as he looks back into the great science hidden in the RES archives.

 The Incomplete Digestion of Proteins Taken up by Macrophages

Is there any correlation between the partial digestion of antigens within macrophages and delayed hypersensitivity? How and where does part of the ingested antigen escape complete degradation? Is the persistent antigen localized on the cellular membrane, in endocytic vesicles, or in pino-lysosomes? Is incomplete digestion the result of an uptake ability that exceeds the capacity for digestion? Does the lysosomal hydrolase content of macrophages influence intracellular digestion? Wiener and Curelaru in 1972 answered the last two questions when they studied the ingestion and digestion of two radiolabeled antigenic proteins, heat-agglutinated human serum albumin (HSA) and keyhole limpet hemocyanin (KLH), with ¹²⁵I or ¹³¹I by cultured mouse peritoneal macrophages. They observed that the uptake of these proteins was comparable to the level of certain lysosomal hydrolases, such as cathepsin D, in the macrophages. Also, the level of the undigested protein in the macrophage culture is independent of the amount endocytosed. Lastly, Wiener and Curelaru established a relationship between the degree of protein degradation and the macrophage content of certain acid hydrolases. In their words, “It seems that after their uptake, a constant part of the proteins is channeled into a pino-lysosomal compartment in which any amount of these macromolecules entering it can be hydrolyzed. The remaining endocytosed material is apparently shunted to sites where complete proteolysis is not carried out. The stimulated protein digestion in lysosome-rich macrophages might be due to an expansion of the proteolytic compartment”.