title: Bovine lactoferrin can be taken up by the human intestinal lactoferrin receptor and exert bioactivities.
abstract: 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.
  
  
  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 I and Fe 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.
authors.affiliation: Department of Nutrition, University of California, Davis, CA 95616, USA. bllonnerdal@ucdavis.edu
authors.forename: Bo
authors.initials: B
authors.lastname: Lönnerdal
authors.forename: Rulan
authors.initials: R
authors.lastname: Jiang
authors.forename: Xiaou
authors.initials: X
authors.lastname: Du
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D007223:Infant; D041943:Infant Formula / Q000737:chemistry; D020382:Interleukin-18 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D007501:Iron / Q000378:metabolism; D007781:Lactoferrin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D037102:Lectins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D020382:Interleukin-18; C490098:LTF protein, human; D037102:Lectins; D008070:Lipopolysaccharides; D053773:Transforming Growth Factor beta1; D007501:Iron; D007781:Lactoferrin