Uptake of ingested bovine lactoferrin and its accumulation in adult mouse tissues.

Lactoferrin is a glycoprotein with antimicrobial and immunoregulatory properties, which is found in milk, other external secretions, and in the secondary granules of neutrophils. The present study examined the time course of uptake and the pattern of tissue accumulation of bovine lactoferrin (bLf) following intragastric intubation of a single dose to adult naïve mice or to mice daily fed bLf for 4 weeks. Following ingestion, bLf was transferred from the intestine into peripheral blood in a form with intact molecular weight (80 kDa) and localized within 10 to 20 min after oral administration in the liver, kidneys, gall bladder, spleen, and brain of both groups of mice. Immunoreactive bLf could also be detected in the luminal contents of the stomach, small intestine and colon 1 h after intragastric intubation. Interestingly, serum and tissue accumulation of bLf was approximately 50% lower in mice chronically fed this protein than in those given only the single oral dose. Furthermore, significant levels of bLf-specific IgA and IgG antibodies as well as bLf-containing IgA- and IgG immune complexes were detected in mice chronically fed bLf but not in those fed only once. Taken together, these results indicate that bLf resists major proteolytic degradation in the intestinal lumen and is readily absorbed in an antigenic form in blood and various mouse tissues. Chronic ingestion of lactoferrin reduces its uptake, probably through mechanisms such as immune exclusion, which minimize potential harmful reactions to food products.

Peanut-lupine antibody cross-reactivity is not associated to cross-allergenicity in peanut-sensitized mouse strains.

BACKGROUND: Peanut hypersensitivity is one of the most common food allergies and one of the most common causes of death by food anaphylaxis in children and adults. Cross-reactivity of peanut-specific antibody (Ab) with other legumes is frequently demonstrated but it still remains to be demonstrated whether these responses could lead to clinical signs of cross-allergenicity. OBJECTIVE: We sought to evaluate peanut-specific serum IgE and IgG1 antibody (Ab) responses and anaphylactic reaction in mice strains and to assess both cross-reactivity and cross-allergenicity of peanut and lupine. METHODS: Four mice strains (i.e., C3H, BALB/c, CBA and SJL) were sensitized to peanut by intraperitoneal (ip) injection of crude peanut protein extract with alum. Other groups were given oral peanut extract without adjuvant. Peanut-specific antibodies (Abs) and anaphylactic responses to peanut challenge were examined. RESULTS: The C3H, CBA (H-2(k)) and BALB/c (H2-(d)) mice exhibited high levels of peanut-specific serum IgE, IgG1 Ab responses after the intra-peritoneal sensitization. Only the two strains of mice in the H-2(k) background developed anaphylactic symptoms upon intra-peritoneal challenge with crude peanut protein extract. While cross-reactivity of peanut and lupine was confirmed by ELISA, no clinical symptom of cross-allergenicity was seen after challenge with lupine. Mice that were given oral peanut showed only increase in peanut-specific IgG2a, but no IgE or IgG1 Abs and failed to develop anaphylactic reactions following injection of either peanut or lupine protein. CONCLUSION: These results show that mice of different genetic backgrounds can be sensitized to peanut by ip injection to develop anti-peanut Abs that cross react with lupine. In addition, cross-allergenicity may not directly correlate with the presence of cross-reactive Abs since no clinical symptoms of cross-allergenicity was seen after ip challenge with lupine.

The mode of oral bovine lactoferrin administration influences mucosal and systemic immune responses in mice.

Food protein intake interacts with the immune system. In earlier nutritional and immunological studies, nutrients, particularly milk whey proteins, were generally administered in soluble form and by gavage. However, orogastric intubation does not represent a natural way of ingesting nutrients such as lactoferrin (Lf). We examined how different modes of oral administration of Lf could affect the regulatory effect of this molecule on intestinal and systemic immune responses. Groups of 10 female BALB/c mice were administered Lf daily for 6 wk. To address the influence of the oral modes of administration, mice were given Lf either in solution, by gastric intubation or in the drinking water, or as a powder, by buccal deposition or in the diet. Mucosal and systemic immune responses, including specific immunoglobulin (Ig) secretion, cell proliferation, and cytokine production, were analyzed and compared with those of naïve mice given water under the same conditions or positive control mice that were administered Lf by i.m. injection. The addition of Lf to the drinking water had no visible effect on the immune status. Gastric intubation, single buccal doses, and continuous doses of Lf in the diet stimulated transient systemic and intestinal antibody responses against Lf. All of these oral modes of Lf exposure biased mucosal and systemic T-cell responses toward Thelper (Th)2-types and elevated IgA production by mucosal cells. However, the less natural gastric intubation also promoted Th1-type responses as evidenced by serum IgG(2a) antibodies and the secretion of Th1 cytokine by mucosal and systemic T cells in vitro. Thus, one should carefully consider the oral mode of administration for understanding regulation of immune responses by food proteins such as Lf.