Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Lactoferrin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources
PubMed1993

Iron acquisition by Helicobacter pylori: importance of human lactoferrin.

Helicobacter pylori is known to be an etiologic agent of gastritis and peptic ulcer disease in humans. However, the mechanism by which this organism acquires iron has not been studied. For this investigation, H. pylori was grown in iron-restricted medium. Siderophore production was not detected by chemical assays, and the strains were unable to use enterochelin and pyochelin for growth in low-iron media. Human lactoferrin supported full growth of the bacteria in media lacking other iron sources, but neither human transferrin, bovine lactoferrin, nor hen ovotransferrin served as a source for iron. Since lactoferrin was found in significant amounts in human stomach resections with superficial or atrophic gastritis, the iron acquisition system of H. pylori by the human lactoferrin receptor system may play a major role in the virulence of H. pylori infection.

Animals↗
PubMed1995

Giardicidal activity of lactoferrin and N-terminal peptides.

Human and bovine lactoferrins and their derived N-terminal peptides were giardicidal in vitro. Fe3+, but not Fe2+, protected trophozoites from both native lactoferrin and peptides, although the latter lack iron-binding sites. Other divalent metal ions protected only against native lactoferrin. Log-phase cells were more resistant to killing than stationary-phase cells. These studies suggest that lactoferrin, especially in the form of the N-terminal peptides, may be an important nonimmune component of host mucosal defenses against Giardia lamblia.

Animals↗
PubMed1996

Expression of the CopB outer membrane protein by Moraxella catarrhalis is regulated by iron and affects iron acquisition from transferrin and lactoferrin.

The amino acid sequence of the cell-surface-exposed, 81-kDa CopB outer membrane protein of Moraxella catarrhalis was found to be similar to those of TonB-dependent outer membrane proteins of other gram-negative bacteria. Expression of CopB was affected by the availability of iron in the growth medium, and the extent of overexpression of CopB in response to iron limitation varied widely among the M. catarrhalis strains tested. Wild-type M. catarrhalis strains were found to be able to utilize ferric citrate, transferrin, lactoferrin, and heme as sources of iron for growth in vitro. However, an isogenic copB mutant was severely impaired in its ability to utilize transferrin and lactoferrin as sole sources of iron for growth, whereas this same mutant grew similarly to the wild-type parent strain when supplied with ferric citrate as the iron source. The copB mutant was not significantly different from its wild-type parent strain in its ability to bind transferrin and lactoferrin. In addition, the wild-type parent strain and the copB mutant exhibited equivalent rates of uptake of 55Fe from ferric citrate. However, the copB mutant was markedly less able than the wild-type strain to take up 55Fe from transferrin and lactoferrin. These results indicate that lack of expression of the CopB protein exerts a direct or indirect effect on the ability of M. catarrhalis to utilize iron bound to certain carrier proteins.

Amino Acid Sequence↗
PubMed2002

Lactoferrin protects rabbits from Shigella flexneri-induced inflammatory enteritis.

Shigella species cause bacillary dysentery in humans by invasion, intracellular multiplication, spread to adjacent cells, and induction of brisk inflammatory responses in the intestinal epithelium. In vitro data suggest that lactoferrin, a glycoprotein present in human mucosal secretions, has a role in protection from bacterial enteric infections. We sought to determine the activity of lactoferrin in vivo, using the concentration present in human colostrum, to investigate its effect on the development of clinical and pathological evidence of inflammation in a rabbit model of enteritis. Lactoferrin protected rabbits infected with Shigella flexneri from developing inflammatory intestinal disease. Typical histological changes in ill animals included villous blunting with sloughing of epithelial cells, submucosal edema, infiltration of leukocytes, venous congestion, and hemorrhage. Lactoferrin at a concentration normally found in human colostrum blocks development of S. flexneri-induced inflammatory enteritis.

Animals↗
PubMed2000

Pathogenic neisseriae can use hemoglobin, transferrin, and lactoferrin independently of the tonB locus.

Redundant TonB systems which function in iron transport from TonB-dependent ligands have recently been identified in several gram-negative bacteria. We demonstrate here that in addition to the previously described tonB locus, an alternative system exists for the utilization of iron from hemoglobin, transferrin, or lactoferrin in Neisseria meningitidis and Neisseria gonorrhoeae. Following incubation on media containing hemoglobin, N. meningitidis IR3436 (tonB exbB exbD deletion mutant) and N. gonorrhoeae PD3401 (tonB insertional mutant) give rise to colonies which can grow with hemoglobin. Transfer of Hb(+) variants (PD3437 or PD3402) to media containing hemoglobin, transferrin, and/or lactoferrin as sole iron sources resulted in growth comparable to that observed for the wild-type strains. Transformation of N. meningitidis IR3436 or N. gonorrhoeae PD3401 with chromosomal DNA from the Hb(+) variants yielded transformants capable of growth with hemoglobin. When we inactivated the TonB-dependent outer membrane hemoglobin receptors (HmbR or HpuB) in the Neisseria Hb(+) variants, these strains could not grow with hemoglobin; however, growth was observed with transferrin and/or lactoferrin. These results demonstrate that accumulation of iron from hemoglobin, transferrin, and lactoferrin in the pathogenic neisseriae can occur via a system that is independent of the previously described tonB locus.

Bacterial Outer Membrane Proteins↗
PubMed1979

Binding and ingestion of human lactoferrin by mouse alveolar macrophages.

59Fe-labelled human lactoferrin was found to be preferentially ingested by mouse alveolar macrophages (MAM) when compared to 59Fe-labelled human transferrin. The cells bound and ingested 125I-labelled iron-saturated and iron-free lactoferrin. The latter was digested faster (t1/2 = 5.8 hours), however, than the iron-saturated compound (t1/2 = 10.5 hours). The constant elimination of the Fe-lactoferrin complex by alveolar macrophages could enhance the bacteriostatic effect of lactoferrin in the pulmonary secretions.

Animals↗
PubMed2002

Antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activities of lactoferrin.

Ovotransferrin (formerly conalbumin) is an iron-binding protein present in birds. It belongs to the transferrin family and shows about 50% sequence homology with mammalian serum transferrin and lactoferrin. This protein has been demonstrated to be capable of delivering iron to cells and of inhibiting bacterial multiplication. However, no antiviral activity has been reported for ovotransferrin, although the antiviral activity of human and bovine lactoferrins against several viruses, including human herpes simplex viruses, has been well established. In this report, the antiviral activity of ovotransferrin towards chicken embryo fibroblast infection by Marek's disease virus (MDV), an avian herpesvirus, was clearly demonstrated. Ovotransferrin was more effective than human and bovine lactoferrins in inhibiting MDV infection and no correlation between antiviral efficacy and iron saturation was found. The observations reported here are of interest from an evolutionary point of view since it is likely that the defensive properties of transferrins appeared early in evolution. In birds, the defensive properties of ovotransferrin remained joined to iron transport functions; in mammals, iron transport functions became peculiar to serum transferrin, and the defensive properties towards infections were optimised in lactoferrin.

Animals↗
PubMed1981

Hemodialysis-induced increase in serum lactoferrin and serum eosinophil cationic protein as signs of local neutrophil and eosinophil degranulation.

Transient reduction in circulating polymorphonuclear granulocytes and eosinophils were observed early in hemodialysis. About a threefold increase in serum-lactoferrin occurred 2 h from the start of hemodialysis. Increments of the serum levels of eosinophil cationic protein (ECP) were observed as early as 1 h after initiation of hemodialysis, reaching maximum levels (about a fourfold increase from initial levels) 1 h later. When fresh blood was circulated through a dialyzer without having a patient in the circuit considerable increases of lactoferrin and ECP were also found. The intracellular contents of lactoferrin and ECP in granulocytes isolated from peripheral blood were unaffected throughout the dialysis period. Sera obtained at different times during dialysis induced no release of granular proteins from isolated granulocytes in vitro. The raised serum concentrations of lactoferrin and ECP during dialysis suggest that a local degranulation of neutrophils and eosinophils may take place probably in the dialyzer.

Adult↗
PubMed1993

Protective effect of lactoferrin on caerulein-induced acute pancreatitis in rats.

In rats we studied the effects of lactoferrin on experimental acute pancreatitis caused by a single subcutaneous injection of 100 micrograms/kg body weight of caerulein. Lactoferrin isolated from human milk was given intraperitoneally to rats immediately after the injection of caerulein. The injection of 100 mg/kg body weight of lactoferrin significantly reduced the elevation of the serum amylase level and pancreatic wet weight; histological alterations of the pancreas were markedly suppressed. These results suggested that lactoferrin had a protective effect on the biochemical and histological alterations in this model.

Acute Disease↗
PubMed1983

Regulation of colony-stimulating activity production. Interactions of fibroblasts, mononuclear phagocytes, and lactoferrin.

Neonatal skin fibroblasts were cultured in supernatants of peripheral blood monocytes that had been cultured with and without lactoferrin. Granulocyte-monocyte colony-stimulating activity (CSA) was measured in supernatants of the fibroblast cultures with normal T lymphocyte-depleted, phagocyte-depleted, low density bone marrow target cells in colony growth (colony-forming unit granulocyte/macrophage) assays. Monocyte-conditioned medium contained a nondialyzable factor that enhanced by 17-50-fold the production of CSA by fibroblasts. The addition of lactoferrin to monocyte cultures reduced the activity of this monokine by 75-100%. Lactoferrin did not inhibit CSA production by monokine-stimulated fibroblasts. We conclude that under appropriate conditions human fibroblasts are potent sources of CSA, that the production of CSA by these cells is regulated by a stimulatory monokine, and that the production and or release of the monokine is inhibited by lactoferrin, a neutrophil-derived putative feedback inhibitor of granulopoiesis. We propose that the major role of mononuclear phagocytes in granulopoiesis is played not by producing CSA, but by recruiting other cells to do so, and that in the steady state, feedback regulation of neutrophil production may occur as a result of a mechanism that inhibits the recruitment phenomenon.

Cells, Cultured↗
PubMed1993

Development of secretory elements in murine tubotympanum: lysozyme and lactoferrin immunohistochemistry.

Secretory activity, particularly of antibacterial agents such as lysozyme and lactoferrin, is an important aspect of the mucosal defense mechanism, and the development of these agents may have a direct bearing on the susceptibility of the ear to infection. In this study, the secretory cells of the murine tubal epithelium were first observed at gestational day 17. Although tubal glands began to develop on gestational day 18, their secretory activity was first shown on postnatal day 3. The number of secretory cells of the tubal epithelium increased rapidly immediately after birth, while that of the tubal glands showed a gradual increase from postnatal day 3. The epithelial secretory cells in the tubotympanum matured at birth, but the tubal glands matured gradually after birth. Lysozyme was first recognized in the epithelial secretory cells on postnatal day 1, while lactoferrin was first detected in the tubal glands on postnatal day 3. Both lysozyme and lactoferrin were co-localized in the serous cells of the tubal glands. The secretion of lysozyme and lactoferrin seemed to reflect the maturation of the secretory cells in the murine tubotympanum.

Alcian Blue↗
PubMed2003

MG2 and lactoferrin form a heterotypic complex in salivary secretions.

Protein-protein interactions are necessary for homeostasis to be maintained and for biological systems to be integrated. Heterotypic complexes occur in saliva, and a complex between MG2 and SIgA has been suggested to promote microbial clearance from the oral cavity. In this study, we used a peptide display library to investigate previously unrecognized heterotypic complexes involving MG2 and other proteins. The library was panned with MG2 12 times, and analyses of clones identified the sequence Ala-Leu-Leu-Cys-, which occurs in salivary lactoferrin. Blotting experiments confirmed that MG2 and lactoferrin form a heterotypic complex in vitro and in vivo. Periodate treatment of MG2 did not affect the interaction. A synthetic lactoferrin peptide containing the motif Ala-Leu-Leu-Cys-blocked the interaction between MG2 and lactoferrin, confirming the specificity of the interaction identified by panning. This complex may enhance the properties of these salivary components in the oral environment.

Adult↗
PubMed2003

Faecal lactoferrin as a predictor of positive faecal culture in south Indian children with acute diarrhoea.

Faecal lactoferrin, an iron-based glycoprotein found concentrated in secondary granules of neutrophils, may serve as a surrogate marker of inflammation in the intestine. We evaluated the usefulness of faecal lactoferrin as a predictor of infection with invasive enteropathogens in 262 children with diarrhoea. Lactoferrin at a dilution of 1:50 had the highest sensitivity for detection not only of conventionally cultured invasive enteropathogens but also of all other enteropathogens. Neither individual clinical symptoms nor the identification of faecal leucocytes by microscopy significantly predicted isolation of invasive enteropathogens from the faeces of children with diarrhoea. Faecal lactoferrin is a simple test which showed promise in predicting which children with diarrhoea are likely to be infected with invasive pathogens and can be incorporated as a screening test before faecal cultures are undertaken in this population.

Acute Disease↗
PubMed1996

Orally administered lactoferrin increases hepatic protein synthesis in formula-fed newborn pigs.

Lactoferrin is a polypeptide which is abundant in colostrum; however, its biologic effect in the neonate is unknown. The objective was to determine the potentially anabolic effect of orally administered lactoferrin on visceral organ growth and protein synthesis in newborn pigs. We studied a total of 18 unsuckled newborn pigs from six litters. Three pigs from each litter were randomly assigned to one of three dietary treatment groups (n = 6) and bottle-fed (10 mL/h) formula, formula containing physiologic levels (1 mg/mL) of added bovine lactoferrin (bLF), or colostrum. After 24 h of feeding, we measured visceral organ protein synthesis in vivo using a flooding dose of [3H]phenylalanine. We also measured visceral organ protein and DNA mass, as well as intestinal hydrolase activities and villus morphology. Hepatic protein synthesis in pigs fed either formula containing bLF or colostrum was similar and in both groups was significantly higher than in pigs fed formula. Splenic protein synthesis was not significantly different in pigs fed either formula or formula containing bLF, but was significantly higher in colostrum-fed animals. There were no significant differences in small intestinal growth, protein synthesis, or hydrolase activities between newborn pigs fed formula, formula containing bLF, or colostrum. Our results demonstrate that feeding formula containing physiologic concentrations of added bLF increased hepatic protein synthesis in newborn pigs, suggesting that colostrumborne lactoferrin serves an anabolic function in neonates.

Administration, Oral↗
PubMed2002

Lactoferrin in the preterm infants' diet attenuates iron-induced oxidation products.

Free radical injury is thought to play a significant role in the pathogenesis of several disease processes in low birth weight premature infants including retinopathy of prematurity and necrotizing enterocolitis. Because iron is a known catalyst in free radical-mediated oxidation reactions, the objectives of the present in vitro studies were to determine whether after exposure to air 1) iron present in infant formula, or that added to human milk or formula as medicinal iron or as iron contained in human milk fortifier, increases free radical and lipid peroxidation products; and 2) recombinant human lactoferrin added to formula or human milk attenuates iron-mediated free radical formation and lipid peroxidation. Before adding medicinal iron to formula and human milk, significantly more ascorbate and alpha-hydroxyethyl radical production and more lipid peroxidation products (i.e. thiobarbituric acid reactive substances, malondialdehyde, and ethane) were observed in formula. After the addition of medicinal iron to either formula or human milk, further increases were observed in free radical and lipid peroxidation products. When iron-containing human milk fortifier was added to human milk, free radicals also increased. In contrast, the addition of apo-recombinant human lactoferrin to formula or human milk decreased the levels of oxidative products when medicinal iron or human milk fortifier was present. We speculate that the presence of greater concentration of iron and the absence of lactoferrin in formula compared with human milk results in greater in vitro generation of free radicals and lipid peroxidation products. Whether iron-containing formula with lactoferrin administered enterally to preterm infants will result in less free radical generation in vivo has yet to be established.

Apoproteins↗
PubMed1996

Promoter-specific activation of mouse lactoferrin gene by epidermal growth factor involves two adjacent regulatory elements.

The mouse lactoferrin gene responded to forskolin, 12-O-tetradecanoyl phorbol-13-acetate, and epidermal growth factor (EGF) stimulation via two adjacent enhancer elements, the cAMP response element (CRE) and EGF response element (EGFRE), collectively referred to as the mitogen response unit. In this report, we examined the minimal promoter and enhancer elements of the mouse lactoferrin gene that are required for EGF-induced transcriptional activation. We found that the CRE and noncanonical TATA box (ATAAA) are the minimal promoter elements for basal activity of the chloramphenicol acetyltransferase (CAT) reporter construct whereas the EGFRE is needed for an additional activity induced by EGF in transiently transfected human endometrial carcinoma RL95-2 cells (RL95-2). The EGFRE, however, did not function in heterologous promoters [SV 40 and thymidine kinase (TK)]. Therefore, EGF-stimulated lactoferrin gene activity is promoter specific in RL95-2 cells. In transiently transfected cells, EGF and forskolin showed synergistic effects on the CAT reporter that contained both response elements. Mutation made at either element or insertion of extra nucleotides between the two elements severely affected EGF-stimulated activity. Nuclear protein prepared from RL95-2 cells formed three complexes (A, B, and C) with the oligonucleotides containing both EGFRE and CRE in electrophoretic mobility shift assay. A new complex (E) was detected with the nuclear protein of EGF-treated cells. By oligonucleotide competition experiments, we demonstrated that the complex E was generated by protein bound to CRE. EGF-induced binding activity could be abolished by calf intestinal alkaline phosphatase but not by the protein synthesis inhibitor, cycloheximide. Therefore, binding of a preexisting phosphoprotein to the CRE region could be one of the requirements for EGF-induced mouse lactoferrin gene promoter activity.

Animals↗
PubMed1992

Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse.

The 5'-flanking region of the human lactoferrin gene was isolated from a human placental genomic library. This genomic clone contains a 16-kilobase pair (kbp) insert and produces seven fragments when digested with the SacI restriction enzyme. We sequenced one of the fragments that comprises 1294 bp of the 5'-flanking sequence, 79 bp of the first exon, and 690 bp of the first intron. A major transcription start site was mapped by primer extension. The region immediately upstream from the transcription initiation site following the first exon is abundant in G and C nucleotides. In the promoter and 5'-flanking region within a 300-bp stretch (-465 to -165) of the DNA, we found a noncanonical TATA box (ATAAA), CAAT-like sequence (CAAC) and sequences homologous to the consensus SP1 binding site, Pu.1/Sp.1 binding element (PU box), two half-palindromic estrogen response elements (EREs; GGTCA), an imperfect ERE (GGTCAAGGCGATC), and a sequence resembling the chicken ovalbumin upstream promoter transcription factor (COUP-TF) binding site (GTCTCACAGGTCA). The COUP-TF binding site and the imperfect ERE shared five nucleotides (GGTCA). With the exception of the two half-palindromic EREs, the elements with very well matched sequences were also found in the corresponding positions in the mouse lactoferrin gene. The synthetic oligonucleotide, including the 26 bp of COUP/ERE sequence, was cloned before the SV40 promoter in a chloramphenicol acetyltransferase reporter construct. These chimeric plasmids were transiently transfected into human endometrium carcinoma RL95-2 cells to assess hormone responsiveness. We found that the COUP/ERE element acted as an enhancer in response to estrogen stimulation. In vitro DNase I footprinting analysis showed binding of the estrogen receptor on the imperfect ERE. In contrast to the mouse lactoferrin COUP/ERE element, COUP-TF does not interact with this element, as demonstrated by band shift assay and site-directed mutagenesis. Therefore, the molecular mechanisms of the estrogen action that govern the lactoferrin gene expression differ between mouse and human.

Amino Acid Sequence↗
PubMed2000

Recombinant human lactoferrin is effective in the treatment of Helicobacter felis-infected mice.

Recombinant human lactoferrin possesses in-vitro antibiotic and anti-inflammatory activity similar to the native form. It was tested for in-vivo activity in mice infected with the gastritis-inducing bacterium Helicobacter felis. A two-week course of treatment with lactoferrin was sufficient to partially reverse both infection-induced gastritis and the infection rate, and fully reverse gastric surface hydrophobicity changes. A comparison of lactoferrin with amoxicillin and standard triple therapy revealed no differences in infection rate. These results show that recombinant human lactoferrin is effective in a mouse model of Helicobacter infection, and support further testing of this promising agent for this application.

Amoxicillin↗