title: Suppression of mouse myelopoiesis by administration of human lactoferrin in vivo and the comparative action of human transferrin.
abstract: 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 micrograms to 10(-4) micrograms lactoferrin per mouse, with loss of activity at 10(-5) micrograms. The suppressive effect of lactoferrin on cycle status of CFU-GM required concentrations of 10 micrograms 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.
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D003115:Colony-Stimulating Factors / Q000502:physiology; D006410:Hematopoiesis / Q000187:drug effects*; D006358:Hot Temperature; D006801:Humans; D007501:Iron / Q000494:pharmacology; D007781:Lactoferrin / Q000008:administration & dosage* / Q000494:pharmacology; D007782:Lactoglobulins / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D014168:Transferrin / Q000494:pharmacology*
chemical_list: D003115:Colony-Stimulating Factors; D007782:Lactoglobulins; D014168:Transferrin; D007501:Iron; D007781:Lactoferrin