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Lactoferrin (LF) is an iron-binding glycoprotein present in the cytoplasmic granules of neutrophils and in external secretions of mammals. Although the biological role of human and bovine lactoferrin has been extensively studied, there is still uncertainty as to the nature and function of lactoferrin receptors. We recently determined that methyl-α-D-mannopyranoside given intraperitoneally (i.p.) could suppress the adjuvant activity of LF in the generation of delayed-type hypersensitivity (DTH) to ovalbumin (OVA). We concluded that the lactoferrin effects in DTH are mediated by carbohydrate-recognizing receptors like the mannose receptor (MR). This study indicates that subcutaneous (s.c.) administration of very small doses of the Man-bovine serum albumin (Man-BSA) complex, together with a sensitizing dose of the antigen, gives the same effects as i.p. administration of methyl-α-D-mannopyranoside. The latter is also a blocker of MR, although of a much lower affinity to the receptor than Man-BSA. The blocking of the adjuvant effect of LF by the Man-BSA complex (when given together with the sensitising dose of antigen) suggests that the function of antigen-presenting cells in the skin (presumably immature dendritic cells expressing MR) is inhibited. The results of our study indicate that a receptor with an affinity for mannose is essential for the mediation of adjuvant lactoferrin function in the generation of DTH.
We compared the susceptibility to viral infection of splenocytes, isolated from young versus old CBA mice, and evaluated the antiviral actions of lactoferrin in splenocytes infected with Encephalomyocarditis virus (EMCV). Recombinant mouse lactoferrin (rmLF) and bovine lactoferrin (bLF) were used. There were no differences in the susceptibility to EMCV infection in the studied age categories. Both types of lactoferrins were protective in young and old mice. The study confirmed the undisturbed viral resistance in old mice and the protective actions of lactoferrin in viral infection. The antiviral action of the homologous mouse lactoferrin was demonstrated for the first time.
The aim of this study was to evaluate protective effects of glycomacropeptide (GMP), a kappa casein-derived peptide, in experimentally induced endotoxemia or bacteremia in mice. The results showed that BALB/c mice, given intraperitoneally (i.p.) GMP, 24h before intravenous (i.v.) injection of a high dose of lipopolysaccharide (LPS) from Escherichia coli, strongly inhibited serum levels of tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6), measured 2h later by bioassays. In addition, GMP, administered 24h before infection of CBA mice with a sublethal dose of E. coli, significantly lowered the number of bacterial cells in the spleen. The analysis of main blood cell types in mice pretreated 24h prior to infection with GMP revealed significant increase in the content of granulocytes and immature neutrophils. We, therefore, postulate, that induction of myelopoiesis by GMP may be a primary cause of the increased clearance of bacteria during the development of bacteremia in mice.
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