Identification of transferrin as the major plasma carrier protein for manganese introduced orally or intravenously or after in vitro addition in the rat.

It is known that the metabolic handling of manganese (Mn) introduced via the diet or by intravenous injection is quite different. We hypothesized that this difference could be due in part to different proteins carrying Mn in plasma that could affect tissue uptake and retention. To test this idea, 54Mn was administered orally or intravenously to rats, and blood samples were taken by cardiac puncture at various time points postdosing. Plasma proteins were separated using fast protein liquid chromatography with a combination of anion exchange and gel filtration columns. Using these methods, independent of the route of 54Mn administration, transferrin was identified as the major Mn-binding protein in plasma. The identity was further confirmed by SDS-polyacrylamide gradient gel electrophoresis and Western blotting. These results conclusively show that 54Mn in plasma is carried by transferrin, regardless of route of administration and time postdosing.