The Monocytic Receptor for Lactoferrin and its Involvement in Lactoferrin-Mediated Iron Transport
Several studies suggest biological functions of the iron-binding neutrophilic glycoprotein lactoferrin that imply an initial interaction with cells from the monocyte/macrophage family. Among these, an important role of lactoferrin as responsible for the inflammatory-induced blood hyposideremia and accumulation of iron in the monocyte/macrophage system has been suggested mainly based on experiments in rodents.
In a series of experiments we have examined the binding of human lactoferrin to human monocytes. We have demonstrated the presence of a receptor binding including a high-affinity component and a low-affinity component. The affinity of the binding is compatible with a biological significance of this receptor (KD is about 10-8 M, and the number of receptors about 106 per cell). More than 90 % of the lactoferrin will dissociate from the cell. The binding is not truly reversible since lactoferrin will lose its receptor-binding property after dissociation from the cell. The only observed change in the molecule is a small decrease in isoelectric point from 8.9 to 8.8.
Lactoferrin is able to translocate at least 50 % of its bound iron to intracellular ferritin in monocytes. These findings are compatible with the idea that lactoferrin might be involved in the pathogenesis of the disturbances in iron metabolism observed during inflammation.
KeywordsZinc Depression Saccharide Corticosteroid Polyethylene
Unable to display preview. Download preview PDF.
- 1.Sørensen M., Sørensen SPL, (1939) The proteins in whey. CR Trav Lab Carlsberg 23: 55–99.Google Scholar
- 4.Matzsumoto A, Yoshima H, Takasaki S, Kobata A (1982) Structural study of the sugar chains of human lactoferrin: Finding of four novel complex-type asparagine-linked sugar chains. J Biochem 91:143–155.Google Scholar
- 7.Masson PL, Heremans JF. (1966) Studies on lactoferrin, the iron-binding protein of secretions. Prot Biol. Fluids 14: 115–124.Google Scholar
- 12.Zucalli JR, Broxmeyer HE, Morse C.(1989) Lactoferrin decreases monocyte-induced fibroblast production of myeloid-stimulating activity by suppressing monocyte release of interleukin-1. Blood 74:1531–1536.Google Scholar
- 25.Birgens HS, Karle K, Hansen NE, Kristensen L0.(1984) Lactoferrin binding to peripheral human leukocytes. Prot Biol Fluids 31:145–148.Google Scholar
- 33.Adayemi EO, Hodgson, HJF.(1988) Augmented release of human leukocyte lactoferrin (and elastase) during coagulation. J Clin Lab Immunol 27:1–4.Google Scholar
- 34.Hansen NE, Karle H, Andersen V, Malmquist J, Hoff GE. (1976). Neutrophilic granulocytes in acute bacterial infection. Sequential studies on lysozyme, myeloperoxidase and lactoferrin. Clin Exp Med 26: 463–468.Google Scholar
- 40.Mazurier J, Metz-Boutigue MH, Joliés J, Spik G, Montreuil J, Joliés P. (1983) Human lactotransferrin: Molecular, functional and evolutionary comparisons with human transferrin and hen ovotransferrin. Experientia 135-141.Google Scholar
- 43.Moguilevsky N. Masson PL, Courtoy PJ.(1987) Lactoferrin uptake and iron processing into macrophages: a study in familial haemochromatosis. Brit J Haematol 66:129–136.Google Scholar
- 49.Lee GR.(1983) The anemia of chronic disease. Sem Hematol 20:61–80.Google Scholar