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Bovine Lactoferrin Can Be Taken Up by the Human Intestinal Lactoferrin Receptor and Exert Bioactivities

Lönnerdal, Bo; Jiang, Rulan; Du, Xiaou

Journal of Pediatric Gastroenterology and Nutrition: December 2011 - Volume 53 - Issue 6 - p 606–614
doi: 10.1097/MPG.0b013e318230a419
Original Articles: Hepatology and Nutrition

Objective: Human lactoferrin (hLF), a major protein in human milk, has been shown to exert multiple biological activities. To achieve some of the benefits of breast-fed infants, we investigated the feasibility of adding commercially available bovine LF (CbLF) to infant formula.

Subjects and Methods: An intestinal enterocyte model (Caco-2 cells) was used to compare the ability of bovine LF (bLF) purified by our laboratory and CbLF with hLF to resist digestion, bind to the receptor, and exert bioactivities, including cellular proliferation, differentiation, interleukin 18 secretion, and transforming growth factor-β1 expression.

Results: bLf and CbLF, which are partially iron (Fe)-saturated, can bind additional Fe, partially resist digestion either dissolved in phosphate buffered saline or in the presence of infant formula at conditions similar to those of the infant gastrointestinal tract, and bind to Caco-2 cells in a manner similar to hLF. bLF and CbLF, as well as bound Fe, also are internalized by Caco-2 cells, as demonstrated by 125I and 59Fe labeling, albeit to somewhat less of an extent than hLF. CbLF promoted cell proliferation and differentiation to an extent similar to that of bLF and hLF, but these effects were not seen when the LF samples were saturated with Fe (holo-LF). Native forms of hLF and bLF significantly increased expression of transforming growth factor-β1, and holo-forms of LFs stimulated interleukin 18 secretion significantly, with the highest results for CbLF.

Conclusions: CbLF is biologically active and is likely to exert several of the bioactivities of hLF if added to infant formula.

Department of Nutrition, University of California, Davis, CA.

Address correspondence and reprint requests to Professor Bo Lönnerdal, Department of Nutrition, University of California, Davis, CA 95616 (e-mail:

Received 18 February, 2011

Accepted 29 July, 2011

The study was supported by an unrestricted grant from FrieslandCampina Domo, Netherlands.

The authors report no conflicts of interest.

Copyright 2011 by ESPGHAN and NASPGHAN