Lactoferrin (Lf), a major iron-binding protein in human milk, has been suggested to have multiple biological roles such as facilitating iron absorption, modulating the immune system, embryonic development, and cell proliferation. Our previous binding studies suggested the presence of a specific receptor for Lf (LfR) in the small intestine of newborn infants, which may facilitate iron absorption. We here report the cloning and the functional expression of the human intestinal LfR and the evidence of its involvement in iron metabolism. The entire coding region of the LfR cDNA was cloned by PCR based on amino acid sequences of the purified native LfR (nLfR). The recombinant LfR (rLfR) was then expressed in a baculovirus-insect cell system and purified by immobilized human Lf (hLf) affinity chromatography where binding of hLf to the rLfR was partially Ca(2+) dependent. The apparent molecular mass was 136 kDa under nonreducing conditions and 34 kDa under reducing conditions. 125I-hLf bound to the rLfR with an apparent K(d) of approximately 360 nM. These biochemical properties of the rLfR are similar to those of the nLfR. RT-PCR revealed that the gene was expressed at high levels in fetal small intestine and in adult heart and at lower levels in Caco-2 cells. PI-PLC treatment of Caco-2 cells indicated that the LfR is GPI anchored. In Caco-2 cells transfected with the LfR gene, 125I-hLf binding and 59Fe-hLf uptake were increased by 1.7 and 3.4 times, respectively, compared to those in mock-transfected cells. Our findings demonstrate the presence of a unique receptor-mediated mechanism for nutrient uptake by the newborn.

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Objectives: Lactoferrin (LF) and lactoperoxidase (LPO) are present in human saliva. LF has been demonstrated to show antibacterial and antiviral activities. In saliva, LPO catalyzes the hydrogen peroxide-dependent oxidation of thiocyanate to hypothiocyanite that exhibits antimicrobial and antiviral properties. A randomized, open-label, parallel-group clinical trial was conducted to examine the effectiveness of sucking tablets containing LF and LPO (LF+LPO) in alleviating symptoms of the common cold and/or influenza infection. Methods: A total of 407 subjects were randomized into two groups, treatment and non-treatment groups, and each group was further classified into subgroups habitually wearing a face mask, washing their hands, or gargling. The common cold, influenza, and gastrointestinal symptoms were used to evaluate the effectiveness, and the incidence and duration of symptoms were statistically analyzed. Results: The incidence and duration of common cold, gastrointestinal symptoms, and influenza infection were not statistically different between treatment and non-treatment groups. LF+LPO tablets were moderately effective in reducing the incidence and duration of common cold symptoms in the subgroup that did not gargle and especially to shorten significantly the duration of fever higher than 38°C in the subgroup that did not wear a face mask. Conclusion: The results suggested that the effect of ingestion of the tablet is not obvious in alleviating common cold symptoms but may be helpful when the subjects do not follow precautionary measures such as gargling and the use of a protective face mask.

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