Production of TCH (Vitamin B,2 Transport Protein) by Mouse Mononuclear Phagocytes

The role of the mononuclear-macrophage system in the production of transcobalamm II (TCII), the vitamin B12 transport protein that delivers the vitamin to the tissues, was investigated in mice. Of all the organs examined for TCII content in unstimulated mice, highest TCll levels were found in the bone marrow. A considerable amount of TCll was present in peripheral blood monocytes. Small amounts of TCII were present in peritoneal exudate cells (PEC) and in the spleen. TCII was undetectable in the thymus and in lymph nodes. Following a single intraperitoneal injection of thioglycolate (TG), a significant increase of TCII concentration was observed in PEC, with a concomitant drop of TCII in the bone marrow. Cultures of PEC harvested from unstimulated and TG-stimulated mice synthesized and secreted considerable amounts of TCll into the medium. After a lag period of several hours the concentration of TCll in the culture mcdi urn increased constantly throughout the entire period of incubation (5-7 days). PEC from stimulated and unstimulated mice were separated into adherent and nonadherent populations. Only the adherent cells, i.e., the macrophages, were consistently found to produce TCII in vitro. These findings show that macrophages produce and secrete TCII. Macrophages, however, did not contain R binders (TCI and TCIII). The observation that concomitant with the rise of TCll in PEC following stimulation there was a marked fall of TCII in the bone marrow indicates that TCII is produced by precursors of mononuclear-macrophage cells in the bone marrow that migrate to the periphery.