Disease relevance of LTF

• Several regions of human LF have been expressed and purified as thioredoxin-fused proteins in Escherichia coli [1].
• Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein [1].
• Specificity of the lactoferrin and transferrin receptors in Neisseria gonorrhoeae [2].
• Characterization of the human transferrin and lactoferrin receptors in Haemophilus influenzae [3].
• Analysis of the immunological responses to transferrin and lactoferrin receptor proteins from Moraxella catarrhalis [4].

Psychiatry related information on LTF

• Lactoferrin expresses in a variety of tissues and involves in various aspects of host defense mechanisms [5].
• The shape of the parahippocampal surface of LTF may be of importance in assessment of the Alzheimer's disease pathology [6].
• Comparisons were made with: (1) symptom scores; (2) olfaction changes; and (3) nasal secretion levels of histamine, tryptase, leukotriene C4, serum albumin (a marker of vascular permeability), lactoferrin (a marker of local glandular secretion), and inflammatory cells in nasal scrapings [7].
• Neuronal cytoplasmic staining with lactotransferrin antibodies, was observed in a subpopulation of pyramidal neurons in normal aging, and was more pronounced in Alzheimer's disease, Guamanian cases, Pick's disease, and particularly in Down syndrome [8].
• The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network [9].

High impact information on LTF

• Particular emphasis is put on milk proteins such as lactoferrin, casein, and whey proteins, but phytate in soy formula is also discussed [10].
• Lactoferrin deficiency associated with altered granulocyte function [11].
• Lactoferrin, an iron-binding glycoprotein found in high concentrations in human milk and other epithelial secretions and in the secondary (specific) granules of neutrophils, is thought to be responsible for primary defence against microbial infection, mainly as a result of lactoferrin sequestration of iron required for microbial growth [12].
• Why diabetes is associated with abnormally high susceptibility to infection remains unknown, although two major antibacterial proteins, lysozyme and lactoferrin, have now been shown to specifically bind glucose-modified proteins bearing advanced glycation end products (AGEs) [13].
• Many other functions have been attributed to lactoferrin, including immunomodulation and cell growth regulation (reviewed in ref. 4). Some of these functions appear to be at least in part independent of the iron-binding activity of lactoferrin [12].

Chemical compound and disease context of LTF

• Lactoferrin (Lf), a LPS-chelating glycoprotein, protects animals against septic shock [14].
• We have investigated Lf immunoexpression as well as its biological meaning in 71 formalin-fixed, paraffin-embedded surgical samples of endometrial carcinomas (EC); 64 EC were endometrioid type, whereas 7 were non-endometrioid carcinomas [15].
• Its expression was restored by treatment with 5-aza-2'-deoxycytidine (5-aza-dC), trichostatin A (TSA) or a combination of both in a subset of lung cancer cell lines without LTF expression [16].
• Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites [17].
• Lactoferrin-lipopolysaccharide interaction: involvement of the 28-34 loop region of human lactoferrin in the high-affinity binding to Escherichia coli 055B5 lipopolysaccharide [18].

Biological context of LTF

• MPO cytochemistry was also associated with immunologic detection of LF [19].
• Further deletion analysis identified 33 amino acid residues as the minimum binding site in the carboxyl region of LF, and the binding specificity of these 33 amino acids was also confirmed by using 33 maltose-binding protein-fused amino acids [1].
• Regulation of human bone marrow lactoferrin and myeloperoxidase gene expression by tumor necrosis factor-alpha [20].
• LF and MPO RNA levels were analyzed by Northern blots using, respectively, a 650-bp insert from the plasmid pHL41, and a 2.3-kb insert from the plasmid pMPO2 as probes [20].
• PMA induced exocytosis of lactoferrin, the specific granule marker, but not of myeloperoxidase, the azurophil granule marker [21].

Anatomical context of LTF

• There was a greater increase in urine concentrations of MPO and LTF, 12.3 and 3.5 times after exercise, respectively, suggesting that neutrophil activation occurred and that renal clearance exceeded the increase in plasma concentrations [22].
• In the bone marrow, myeloblast and promyelocyte granulations were not stained and LF-containing granules appeared at the myelocyte stage [19].
• No other neutrophil organelles displayed labeling for LF; other blood cells also were unreactive for LF [19].
• Binding of lactoferrin and transferrin to the human promonocytic cell line U937. Effect on iron uptake and release [23].
• Immobilized lactoferrin is a stimulus for eosinophil activation [24].

Associations of LTF with chemical compounds

• We examined the potential for lactoferrin, a multifunctional glycoprotein present in the airway surface liquid, to activate eosinophils [24].
• Pretreatment of the lactoferrin with peptide N-glycosidase F or addition of heparin or chondroitin sulfate to the incubation contents had no or only a minimal effect on the activity of immobilized lactoferrin [24].
• The effect of the purple acid phosphatases with binuclear iron centers (uteroferrin and bovine spleen phosphatase) on hydroxyl radical formation by iron-catalyzed Haber-Weiss-Fenton chemistry has been compared to that of lactoferrin and transferrin [25].
• Binding of lactoferrin was not inhibited by 30 mM glucose or fucose nor by incubating the cells with heparinase [23].
• This can be explained by the fact that lactoferrin and transferrin carry two Fe(III) atoms per molecule, neither of which are readily reduced by biological reductants [25].

Physical interactions of LTF

• Lactoferrin did not inhibit binding of transferrin, or vice versa [23].
• The availability of pure OVR and LDLR enable us to determine kinetic parameters for the binding of RAP and lactoferrin to these receptors by surface plasmon resonance [26].
• Human lactoferrin interacts with soluble CD14 and inhibits expression of endothelial adhesion molecules, E-selectin and ICAM-1, induced by the CD14-lipopolysaccharide complex [14].
• Lactoferrin-binding activity in Neisseria meningitidis was detected by a solid-phase binding assay with horseradish peroxidase-conjugated human lactoferrin (HRP-lactoferrin) [27].
• K(d) for the CP/LF complex was estimated from Scatchard plot as 1.8 x 10(-6) M [28].

Enzymatic interactions of LTF

• In addition, we speculate that lactoferrin may cleave arginine-rich sequences in a variety of microbial virulence proteins, contributing to its long-recognized antimicrobial properties [17].
• CCAAT displacement protein (CDP/cut) recognizes a silencer element within the lactoferrin gene promoter [29].

Co-localisations of LTF

• Biosynthesis of hCAP-18 was investigated in isolated human bone marrow cells. hCAP-18 was found to colocalize and comobilize with lactoferrin, but not with gelatinase in subcellular fractions [30].
• YKL-40 was found to colocalize and comobilize with lactoferrin (the most abundant protein of specific granules) but not with gelatinase in subcellular fractionation studies on stimulated and unstimulated neutrophils [31].

Regulatory relationships of LTF

• Lactoferrin inhibited cellular uptake of iron from Fe-nitrilotriacetate but not from transferrin [23].
• Surprisingly, unlike the mouse ER, the human estrogen receptor activated and induced expression of lactoferrin estrogen-responsive module-CAT with all the compounds [32].
• Molecular interactions between human lactotransferrin and the phytohemagglutinin-activated human lymphocyte lactotransferrin receptor lie in two loop-containing regions of the N-terminal domain I of human lactotransferrin [33].
• Lactoferrin-induced mitogenesis is also inhibited by an antibody to LRP1 [34].
• Lactoferrin activates macrophages via TLR4-dependent and -independent signaling pathways [35].

Other interactions of LTF

• Freshly isolated CD34+ CB cells were negative for LZ and LF, and only small proportions expressed MPO (4% +/- 2%) or CD68 (3% +/- 1%) [36].
• The binding affinity for lactoferrin (83 nM) was about 4-fold lower than for transferrin (21 nM) [23].
• ANCA in RA patients are directed toward diverse cytoplasmic antigens of the neutrophil, in particular, LF and other, not yet fully characterized polypeptides [37].
• Lactoferrin, another protein with a high affinity for mammalian LRP/alpha 2MR, also binds to OVR and abolishes its interaction with yolk precursors [26].
• Fe acquisition by M.tb within hereditary hemochromatosis macrophages was decreased by 84% from Tf and 92% from Lf relative to that in healthy control macrophages [38].

Analytical, diagnostic and therapeutic context of LTF

• By Western blotting, 21 sera reacted with LF, and 15 reacted with previously unknown polypeptides (7 sera with a 67/66-kd doublet and 8 with a 63/54-kd doublet) [37].
• Eosinophils bound lactoferrin as determined by flow cytometry and by binding of (125)I-labeled lactoferrin [24].
• By using a previously developed spin-trapping system which allows specific on-line detection of superoxide anion (O2-) and .OH production, the impact of MPO and LF release on neutrophil .OH production was compared [39].
• Separation of the granule classes by linear sucrose density gradient centrifugation revealed the loss, from PMA-treated neutrophils, of lactoferrin and the specific granule (D20(20) = 1.89) band usually resolved from normal neutrophils [21].
• MPO and LF can be used in ELISA procedures for the detection of pANCA-related antibodies [40].

References