Purified human lactoferrin was assessed for its influence in vivo in untreated mice and in mice undergoing rebound myelopoiesis after sublethal dosages of Cytoxan. Fully iron-saturated lactoferrin suppressed the numbers of granulocytes and monocytes per femur, the numbers of granulocyte-macrophage progenitor cells (CFU-GM) per femur and spleen, and decreased the cycle status of femoral and splenic CFU-GM. These effects were detected after administration of lactoferrin i.v. or i.p. into untreated and Cytoxan-treated mice. The suppressive effects on cellularity and numbers of CFU-GM per femur were apparent to a greater degree in mice treated with Cytoxan, and the i.v. route appeared preferable to the i.p. route. Heat-treated lactoferrin, inactive in vitro, was inactive in vivo, but iron-depleted (apo-) lactoferrin, inactive in vitro, was active in vivo, suggesting that the apo-lactoferrin acquired the iron in vivo that was necessary to change it into an active form. Titration of the effects of lactoferrin in Cytoxan-treated mice demonstrated a plateau curve of suppression of nucleated cells and CFU-GM per femur with dosages ranging from 100 μg to 10-4 μg lactoferrin per mouse, with loss of activity at 10-5 μg. The suppressive effect of lactoferrin on cycle status of CFU-GM required concentrations of 10 μg or higher. The effects of lactoferrin were reversible with time, with the suppressive influence on cycling status being lost before that on numbers of CFU-GM per femur. Purified human transferrin was also assessed for its influence in mice undergoing rebound myelopoiesis. Transferrin decreased the nucleated cellularity and the number of CFU-GM per femur and per spleen, but had little or no influence on the cycling status of CFU-GM and differed in its temporal effect on myelopoiesis from that of lactoferrin. These results suggest that lactoferrin and transferrin suppress the number of progenitor cells moving into the CFU-GM compartment and lactoferrin suppresses the cycling status of cells within the CFU-GM compartment. These effects are probably mediated by an action on the production of factors necessary for movement of cells into, and cell cycling within, the CFU-GM compartment.
ASJC Scopus subject areas
- Cell Biology