Lactoferrin stimulates colony stimulating factor production in vitro and in vivo.
A physiologic role for lactoferrin (Lf) has been implicated by (1) its antibacterial effect and (2) its involvement as a negative-feedback regulator for colony stimulating factor (CSF) and, therefore, granulocyte production. The isolation and purification of endotoxin-free, species-specific mouse and human Lf have enabled a study of the role of Lf both in vitro and in vivo. Injection of Salmonella typhimurium or LPS into mice resulted in a dose-dependent increase in plasma Lf. Treating normal and neutropenic mice with LPS showed that the plasma Lf level was directly related to the number of granulocytes found in the peripheral blood. The effect of neutropenia did not inhibit release of Lf. By incubating mouse bone marrow and adherent peritoneal cells with 0.1 microM mouse or human Lf in the absence or presence of the prostaglandin synthesis inhibitor, indomethacin (1.0 microM), no evidence could be obtained in support of a negative-feedback regulation of CSF. In fact, rather than an inhibition of CSF, the production of the latter was found to be stimulated from both cell types. Injection of endotoxin-free, mouse Lf (2 mg/animal) into mice at concentrations in the same order of magnitude as that found during bacterial infection, resulted in an increase in CSF production by 12 hours and prior to the increase in bone marrow granulocyte-macrophage progenitor cells (GM-CFC) at 48 hours. The results do not support a negative-feedback regulation of CSF by macrophages. Instead, they can be incorporated into a "demand signal" model for CSF production by macrophages.
Sawatzki
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Department of Transfusion Medicine, University of Ulm, Federal Republic of Germany.
Rich
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D000818:Animals; D001772:Blood Cell Count; D001853:Bone Marrow / Q000502:physiology; D002448:Cell Adhesion; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000528:radiation effects; D006133:Growth Substances / Q000378:metabolism; D007781:Lactoferrin / Q000302:isolation & purification / Q000502:physiology*; D007782:Lactoglobulins / Q000502:physiology*; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009503:Neutropenia / Q000097:blood; D012481:Salmonella Infections, Animal / Q000503:physiopathology; D012486:Salmonella typhimurium; D013154:Spleen / Q000502:physiology; D014916:Whole-Body Irradiation
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007782:Lactoglobulins; D008070:Lipopolysaccharides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007781:Lactoferrin