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* Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Fredrick, MD 21702;
Basic Research Program, Science Applications International Corporation-Frederick, National Cancer Institute-Fredrick, MD 21702; and
Agennix, Houston, TX 77046
Lactoferrin is an 80-kDa iron-binding protein present at high concentrations in milk and in the granules of neutrophils. It possesses multiple activities, including antibacterial, antiviral, antifungal, and even antitumor effects. Most of its antimicrobial effects are due to direct interaction with pathogens, but a few reports show that it has direct interactions with cells of the immune system. In this study, we show the ability of recombinant human lactoferrin (talactoferrin alfa (TLF)) to chemoattract monocytes. What is more, addition of TLF to human peripheral blood or monocyte-derived dendritic cell cultures resulted in cell maturation, as evidenced by up-regulated expression of CD80, CD83, and CD86, production of proinflammatory cytokines, and increased capacity to stimulate the proliferation of allogeneic lymphocytes. When injected into the mouse peritoneal cavity, lactoferrin also caused a marked recruitment of neutrophils and macrophages. Immunization of mice with OVA in the presence of TLF promoted Th1-polarized Ag-specific immune responses. These results suggest that lactoferrin contributes to the activation of both the innate and adaptive immune responses by promoting the recruitment of leukocytes and activation of dendritic cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported, in whole or in part, by federal funds from the Intramural Research Program of the Center for Cancer Research National Cancer Institute, National Cancer Institute, National Institutes of Health and under Contract No. N01-CO-12400.
2 The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. government.
3 Address correspondence and reprint requests to Dr. Joost J. Oppenheim, Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, National Cancer Institute, P.O. Box B, Building 560, Room 31-19, Frederick, MD 21702-1201. E-mail address: oppenhei{at}ncifcrf.gov
4 Abbreviations used in this paper: TLF, talactoferrin; DC, dendritic cell; hLF, human lactoferrin; PBDC, peripheral blood DC; moDC, monocyte-derived DC; Treg, regulatory T lymphocyte; PI, propidium iodide; PTx, pertussis toxin; MCP-1, monocyte chemoattractant protein-1; SLC, secondary lymphoid tissue chemokine.
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