Role of cathepsin D in the degradation of human serum albumin by peritoneal macrophages and veiled cells in antigen presentation.

Murine peritoneal macrophages (PMO) and veiled cells (VC) isolated from the thoracic duct of irradiated lymphadenectomized (MNLX) mice presented intact human serum albumin (HSA) to stimulated T lymphocytes, but VC were not as effective as PMO in presenting the antigen. Pepstatin A significantly inhibited the presentation of HSA by VC. Lysates prepared from PMO degraded [125I]HSA at pH 4.0 to peptides as demonstrated by SDS-polyacrylamide-gel electrophoresis and autoradiography. Degradation was inhibited by pepstatin A, suggesting that cathepsin D might be responsible for processing the antigen. In contrast, lysates prepared from VC did not degrade [125I]HSA. The localization of cathepsin D, by light microscopy, was examined on cytospins of PMO and VC by means of a peroxidase antiperoxidase technique (PAP). Cathepsin D was found in vacuoles in the cytoplasm of PMO and, in some cases, appeared to be bound to some areas of the cell surface, but the enzyme could not be detected in VC.