UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunomodulatory properties of bovine milk and whey have long been documented. The recent advance of whey protein fractionation technology has now allowed us to study the immunobiological properties of some highly purified components of whey, with a view to exploiting their possible industrial and biomedical applications. The effects of fractionated bovine whey proteins on cellular immune responses were therefore examined using a panel of in vitro assays. Both lactoferrin (LF) and lactoperoxidase (LP) were found to inhibit proliferation and interferon-gamma (IFN-gamma) production of ovine blood lymphocytes in response to mitogenic stimulation. However, their effects in a combined fraction or in whey protein concentrate (WPC) were either diminished or eliminated. LF and LP had no effect on lipopolysaccharide (LPS)-induced ovine blood lymphocyte proliferation, production of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF alpha) by ovine bronchoalveolar lavage (BAL) macrophages, major histocompatibility complex (MHC) Class II antigen expression by ovine BAL macrophages and bovine natural killer (NK) cell activity. However, alpha-lactalbumin (alpha LA) exhibited an enhancing effect on IL-1 beta production. It is noteworthy that as bovine whey fractions become progressively more purified, their modulatory effects on the immune response also become more clear-cut. The effects of LF, LP and alpha LA may be eliminated by their combination in whey or by other minor components of whey. Further investigation of industrial applications for whey proteins of high purity is warranted.
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PMID:Effects of purified bovine whey factors on cellular immune functions in ruminants. 922 May 83

In this double-blind, cross-over, placebo-controlled, randomized study, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once in conjunction with placebo and once with granulocyte colony-stimulating factor (G-CSF; 5 microg/kg). In group 1, G-CSF was administered intravenously 2 hours before endotoxin challenge; in group 2, G-CSF was administered subcutaneously 24 hours before endotoxin challenge. In group 1, G-CSF significantly enhanced the release of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptors. In group 2, G-CSF significantly reduced IL-8 concentrations and modestly attenuated TNF and IL-6 levels. In this group, IL-1ra and soluble TNF receptors were enhanced by G-CSF pretreatment and lipopolysaccharide (LPS)-induced soluble TNF receptor release was further augmented, whereas LPS-induced IL-1ra concentrations remained unaltered. Both pretreatments with G-CSF increased LPS-induced peripheral neutrophilia; the expression of CD11b, CD18, and CD67; and the release of elastase and lactoferrin. Both pretreatments also down-regulated neutrophil L-selectin expression and prevented the endotoxin-induced pulmonary neutrophil accumulation during the first 2 hours after endotoxin challenge. These data indicate that two different pretreatments with G-CSF result in differential effects on LPS-induced cytokine release but similar effects on LPS-induced neutrophil activation and changes in expression of cell surface molecules. Finally, regardless of the effects of G-CSF on LPS-induced cytokine release, G-CSF blocks LPS-induced pulmonary granulocyte accumulation.
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PMID:Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans. 926 59

Human lactoferrin (hLF), a protein involved in host defence against infection and excessive inflammation, interacts with heparin, the lipid A moiety of bacterial lipopolysaccharide, human lysozyme (hLZ) and DNA. To determine which region of the molecule is important in these interactions, solid-phase ligand binding assays were performed with hLF from human milk (natural hLF) and N-terminally deleted hLF variants. Iron-saturated and natural hLF bound equally well to heparin, lipid A, hLZ and DNA. Natural hLF lacking the first two N-terminal amino acids (Gly1-Arg2) showed reactivities of one-half, two-thirds, one-third and one-third towards heparin, lipid A, hLZ and DNA respectively compared with N-terminally intact hLF. A lack of the first three residues (Gly1-Arg2-Arg3) decreased binding to the same ligands to one-eighth, one-quarter, one-twentieth and one-seventeenth respectively. No binding occurred with a mutant lacking the first five residues (Gly1-Arg2-Arg3-Arg4-Arg5). An anti-hLF monoclonal antibody (E11) that reacts to an N-lobe epitope including Arg5 completely blocked hLF-ligand interaction. These results show that the N-terminal stretch of four consecutive arginine residues, Arg2-Arg3-Arg4-Arg5, has a decisive role in the interaction of hLF with heparin, lipid A, hLZ and DNA. The role of limited N-terminal proteolysis of hLF in its anti-infective and anti-inflammatory properties is discussed.
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PMID:N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is essential for binding to heparin, bacterial lipopolysaccharide, human lysozyme and DNA. 935 45

The effects were examined of a pepsin hydrolysate of bovine lactoferrin on the proliferation of murine splenocytes. The hydrolysate enhanced [3H]thymidine uptake by splenocytes, but undigested bovine lactoferrin exerted an inhibitory effect. The hydrolysate had the ability to inhibit the blastogenesis that was induced by mitogens such as concanavalin A, phytohemagglutinin, and lipopolysaccharide; inhibition was similar to that with undigested lactoferrin. These results suggested that the hydrolysate contained both immunostimulatory and immunoinhibitory peptides. The stimulatory effect of the hydrolysate in the absence of mitogens was then explored in more detail using nonadherent splenocytes. The proliferative response of splenocytes to the hydrolysate was much greater in the fraction that was enriched with B cells than in the fraction that was enriched with T cells. The hydrolysate did not affect thymocyte proliferation. These data indicated that the adherent cells resembling macrophages and found among the splenocytes were not the target cells of the hydrolysate. The stimulatory effect of the hydrolysate was due to the activation of B cells by the hydrolysate and enhanced immunoglobulin production by splenocytes. Because the hydrolysate also enhanced the proliferation and immunoglobulin A production of Peyer's Patch cells, the immunostimulatory effect of the hydrolysate in vivo was examined using mice that had been orally immunized with cholera toxin. The concentrations of immunoglobulin A conjugated against cholera toxin in bile and in the intestinal contents of mice fed liquid diets containing 1% (wt/vol) lactoferrin hydrolysate were greater than those of mice fed control diets. This result suggested that the use of the lactoferrin hydrolysate is beneficial to enhance mucosal immunity.
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PMID:Immunomodulatory effect of bovine lactoferrin pepsin hydrolysate on murine splenocytes and Peyer's patch cells. 936 Dec 5

Human lactoferrin (hLf), a glycoprotein released from neutrophil granules during inflammation, and the lipopolysaccharide (LPS)-binding protein (LBP), an acute-phase serum protein, are known to bind to the lipid A of LPS. The LPS-binding sites are located in the N-terminal regions of both proteins, at amino acid residues 28 to 34 of hLf and 91 to 108 of LBP. Both of these proteins modulate endotoxin activities, but they possess biologically antagonistic properties. In this study, we have investigated the competition between hLf and recombinant human LBP (rhLBP) for the binding of Escherichia coli 055:B5 LPS to the differentiated monocytic THP-1 cell line. Our studies revealed that hLf prevented the rhLBP-mediated binding of LPS to the CD14 receptor on cells. Maximal inhibition of LPS-cell interactions by hLf was raised when both hLf and rhLBP were simultaneously added to LPS or when hLf and LPS were mixed with cells 30 min prior to the incubation with rhLBP. However, when hLf was added 30 min after the interaction of rhLBP with LPS, the binding of the rhLPS-LBP complex to CD14 could not be reversed. These observations indicate that hLf competes with rhLBP for the LPS binding and therefore interferes with the interaction of LPS with CD14. Furthermore, experiments involving competitive binding of the rhLBP-LPS complex to cells with two recombinant mutated hLfs show that in addition to residues 28 to 34, another basic cluster which contains residues 1 to 5 of hLf competes for the binding to LPS. Basic sequences homologous to residues 28 to 34 of hLf were evidenced on LPS-binding proteins such as LBP, bactericidal/permeability-increasing protein, and Limulus anti-LPS factor.
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PMID:Lactoferrin inhibits the endotoxin interaction with CD14 by competition with the lipopolysaccharide-binding protein. 945

The unique germfree, colostrum-deprived, immunologically "virgin" piglet model was used to evaluate the ability of lactoferrin (LF) to protect against lethal shock induced by intravenously administered endotoxin. Piglets were fed LF or bovine serum albumin (BSA) prior to challenge with intravenous Escherichia coli lipopolysaccharide (LPS), and temperature, clinical symptoms, and mortality were tracked for 48 h following LPS administration. Prefeeding with LF resulted in a significant decrease in piglet mortality compared to feeding with BSA (16.7 versus 73.7% mortality, P < 0.001). Protection against the LPS challenge by LF was also correlated with both resistance to induction of hypothermia by endotoxin and an overall increase in wellness, as quantified by a toxicity score developed for these studies. In vitro studies using a flow cytometric assay system demonstrated that LPS binding to porcine monocytes was inhibited by LF in a dose-dependent fashion, suggesting that the mechanism of LF action in vivo may be inhibition of LPS binding to monocytes/macrophages and, in turn, prevention of induction of monocyte/macrophage-derived inflammatory-toxic cytokines.
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PMID:The protective effects of lactoferrin feeding against endotoxin lethal shock in germfree piglets. 952 62

Lactoferricin includes an 11-amino-acid amphipathic alpha-helical region which is exhibited on the outer surface of the amino-terminal lobe of lactoferrin. Synthetic peptides homologous to this region exhibited potent antibacterial activity against a selected range of both gram-negative and gram-positive bacteria. An analog synthesized with methionine substituted for proline at position 26, which is predicted to disrupt the helical region, abolished antibacterial activity against Escherichia coli and considerably reduced antibacterial activity against Staphylococcus aureus and an Acinetobacter strain. The mode of action of human lactoferrin peptide (HLP) 2 against E. coli serotype O111 (NCTC 8007) was established by using flow cytometry, surface plasmon resonance, and transmission electron microscopy. Flow cytometry was used to monitor membrane potential, membrane integrity, and metabolic processes by using the fluorescent probes bis-1,3-(dibutylbarbituric acid)-trimethine oxonol, propidium iodide, and carbonyl cyanide m-chlorophenylhydrazone, respectively. HLP 2 was found to act at the cell membrane, causing complete loss of membrane potential after 10 min and of membrane integrity within 30 min, with irreversible damage to the cell as shown by rapid loss of viability. The number of particles, measured by light scatter on the flow cytometer, dropped significantly, showing that bacterial lysis resulted. The peptide was shown to bind to E. coli O111 lipopolysaccharide by using surface plasmon resonance. Transmission electron microscopy revealed bacterial distortion, with the outer membrane becoming detached from the inner cytoplasmic membrane. We conclude that HLP 2 causes membrane disruption of the outer membrane, resulting in lysis, and that structural considerations are important for antibacterial activity.
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PMID:Structure-function relationship of antibacterial synthetic peptides homologous to a helical surface region on human lactoferrin against Escherichia coli serotype O111. 959 99

The aim of this investigation was to monitor proliferation and cytokine production by peripheral blood mononuclear cells (PBMC) of patients subjected to cardiac surgery. Another goal was to establish regulatory effects of lactoferrin (LF) on these immune reactions in vitro. PBMC were tested before, during surgery and on day 1 and day 8-10 following operation. In control donors, low spontaneous and phytohemagglutinin (PHA)-induced proliferation of PBMC, as well as lipopolysaccharide (LPS)-induced TNF-alpha secretion was stimulated by LF, but high production of this cytokine was inhibited. In patients, the proliferation of PBMC and the ability to produce IL-6 TNF-alpha by these cells underwent characteristic changes depending on preoperative immune reactivity of patients. In general, low, preoperative reactivity of PBMC showed a tendency to increase within the monitoring period whereas moderate/high responsiveness was diminishing. LF had, in majority of cases, a down-regulatory effect on the proliferative response, best pronounced in patients of high/moderate preoperative response. Similarly, LF exhibited, in general, an inhibitory effect on LPS-induced IL-6 production. In terms of TNF-alpha production, a considerable up-regulatory effect of LF, particularly in low responding patients was of a special interest. In summary, we suggest that LF may play a role in lowering the immune response of patients to surgery and promoting tissue regeneration.
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PMID:Immunological status of patients subjected to cardiac surgery: effect of lactoferrin on proliferation and production of interleukin 6 and tumor necrosis factor alpha by peripheral blood mononuclear cells in vitro. 959 88

In our present work we present the determination of bovine lactoferrin in whey concentrates as they are typically produced by milk and cheese industry after production of cheese. Due to the high total protein content the analysis of whey concentrate samples is difficult and even not possible by using capillary zone electrophoresis with UV detection. To enhance the detection sensitivity we applied a more promising approach by using affinity interactions in combination with laser-induced fluorescence detection. By mixing fluoresceine isothiocyanate (FITC)-conjugated polyanionic lipopolysaccharide with the mostly positively charged lactoferrin we found a significant migration time shift which is clearly dependent on the concentration of the added protein. In the second approach we developed an immunoassay using FITC-conjugated specific antibody against bovine lactoferrin. The results of the immunoassay measurements were compared with data obtained by standard enzyme-linked immunosorbent assay analysis.
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PMID:Determination of the minor whey protein bovine lactoferrin in cheese whey concentrates with capillary electrophoresis. 976 93

The aim of this study was to monitor several immune parameters in 17 healthy volunteers taking orally commercially available capsules containing bovine lactoferrin (BLFT) for 10 days (40 mg of BLFT daily). We determined leukocyte number and content of main blood cell types, spontaneous and phytohemagglutinin A (PHA)-induced proliferation of lymphocytes, plasma levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) as well as spontaneous and lipopolysaccharide (LPS)-induced production of these cytokines in peripheral blood cell cultures. All measurements were performed before, one day and 14 days following cessation of BLFT treatment. We established some, transient drop in the percentage of neutrophils accompanied by an opposite phenomenon with regard to lymphocyte levels. More profound changes were registered in the percentage of other cell types, for example a 100% increase in the level of immature cell forms (bands) was noted. At the same time the percentages of eosinophils and monocytes declined significantly. All these changes were, however, more individual and regulatory, the direction of these changes depended on initial picture of blood cells. Although the proliferative response of lymphocytes showed, on average, a transient decrease, differentiated effects of BLFT treatment were observed depending on initial ability of lymphocytes to proliferate. TNF-alpha serum levels showed a tendency to decrease during the monitoring time, the changes of IL-6 levels were, however, not significant. As in the case of the proliferative response, the treatment with BLFT was regulatory with respect to serum TNF-alpha levels. When we analyzed spontaneous and LPS-induced cytokine production in cell cultures we found that mainly the mean spontaneous response was affected (inhibition). We also observed a typical, regulatory action of BLFT on the level of spontaneously produced IL-6. This kind of regulatory action of BLFT was also found in the case of spontaneously produced TNF-alpha in cell cultures. The influence of other ingredients such as selenium or vitamins, contained in the capsules, cannot be excluded, although our latest data showed that orally taken bovine lactoferrin alone can induce identical changes as BLFT. Taken together, we revealed regulatory effects of oral treatment with commercially available capsules, containing BLFT. The results indicate that oral administration on BLFT-containing capsules may regulate some immune parameters in healthy individuals. In addition, the data suggest that bovine lactoferrin may be applied in clinic to improve the immune status of patients.
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PMID:Immunoregulatory effects of a nutritional preparation containing bovine lactoferrin taken orally by healthy individuals. 977 89

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