Interaction of lactoferrin with mononuclear and colon carcinoma cells

Lactoferrin is known to bind to macrophages/monocytes and intestinal mucosal cells, but the nature and function of these interactions is not clear. We have therefore examined the interaction of lactoferrin in vitro with the promonocytic cell line U937 and with differentiated human colon carcinoma cells. U937 cells bound more lactoferrin than transferrin, although most of the lactoferrin binding was non-specific. Uptake of iron from transferrin was rapid, but uptake from lactoferrin was slow, and may have been due to prior transfer of iron to transferrin in the culture medium as a result of labilisation of iron from membrane-bound lactoferrin. Unlike transferrin, lactoferrin was not internalised by U937 cells. Lactoferrin significantly reduced uptake of non-transferrin-bound iron by the cells, but had no effect on uptake of transferrin-bound iron. Transport of lactoferrin-bound iron across monolayer cultures of differentiated Caco-2 cells in bicameral chambers was similar to that of ferric citrate, while transport of transferrin-bound iron was lower. Lactoferrin and transferrin themselves were not transported, although some proteolytically degraded material did cross the monolayer. Thus lactoferrin, unlike transferrin, is not an important iron donor to monocytic cells, but may instead serve to regulate iron uptake from other sources. It does not seem to enhance iron transport across mucosal cells.