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PubMed1999

Salivary lactoferrin and low-Mr mucin MG2 in Actinobacillus actinomycetemcomitans-associated periodontitis.

Concentrations and output of lactoferrin and of low-Mr mucin MG2 were determined in saliva of subjects suffering from Actinobacillus actinomycetemcomitans-associated periodontal disease and healthy subjects. Periodontal patients were clinically examined and a microbiological sample was taken from the deepest bleeding pockets in each quadrant. The number of viable A. actinomycetemcomitans was determined in the sampled sites of each patient. The MG2 output in the diseased subjects (13.6 microg protein/min) was decreased at least by a factor three compared to periodontal healthy subjects (44.3 microg protein/min). On the other hand, output of lactoferrin was not significantly different in healthy (9.5 microg/min) and diseased subjects (7.6 microg/min). Western analyses demonstrated a higher iron-saturation of lactoferrin in diseased subjects in comparison with the healthy subjects. Lactoferrin degrading enzymes, probably derived from microbial sources, could be detected in saliva of the periodontally diseased subjects, but not in saliva of healthy subjects. The combination of iron-saturation and degradation of lactoferrin suggests that anti-microbial properties of lactoferrin are diminished in periodontitis patients. Moreover, the low concentration of mucin MG2 suggests a decline in mucin defence and consequently a higher susceptibility for oral infection. A negative correlation (r= -0.4, p < 0.05) between the number of subgingival A. actinomycetemcomitans and lactoferrin in saliva suggested that low concentrations of lactoferrin favour the growth of the bacterium. These data indicate that a decline in the salivary defence system might increase the risk for oral infection by A. actinomycetemcomitans.

Actinobacillus Infections↗

PubMed1998

The survival of ingested lactoferrin in the gastrointestinal tract of adult mice.

Lactoferrin is an 80 kDa major protein component of mammalian colostral whey. The antimicrobial active centre of lactoferrin, lactoferricin (Lfcin), may also be an important determinant of the interaction between lactoferrin and specific receptors on lymphocytes. We have documented the survival in vivo of ingested lactoferrin in the gastrointestinal tract of adult mice by surface-enhanced laser desorption/ionization affinity MS. Various kinds of degraded lactoferrin fragments were detected as molecular-ion peaks corresponding to Lfcin after being captured by an affinity capture device, hydrolysis in situ and laser desorption/ionization. No evident molecular-ion peaks of Lfcin were observed upon analysis of faeces from mice fed commercial milk, whereas lactoferrin fragments containing the Lfcin region were detected at concentrations in the order of at least pmol/g in the faeces of mice fed milk enriched with lactoferrin at 40 mg/ml. These results suggest that ingested lactoferrin would survive transit through the gastrointestinal tract as partially degraded forms containing the receptor-binding region(s) as well as the antimicrobial active centre.

Animals↗

PubMed2000

Neutrophil lactoferrin release induced by IgA immune complexes differed from that induced by cross-linking of fcalpha receptors (FcalphaR) with a monoclonal antibody, MIP8a.

The human IgA Fc receptor (FcalphaR, CD89) plays an important role in host defence against invading pathogens. To study the properties of the receptor, 12 MoAbs, namely, MIP7c, MIP8a, MIP9a, MIP10c, MIP11c, MIP14b, MIP15b, MIP38c, MIP59c, MIP65c, MIP68b and MIP71a, were generated. The inhibitory effects of the antibodies on FcalphaR functions were tested. Three of the antibodies, MIP7c, MIP8a and MIP59c, were able to block up to 90% of soluble FcalphaR binding to IgA-coated beads and 70-80% of neutrophil phagocytosis of IgA immune complexes (IC). MIP8a could also inhibit IgA IC-induced neutrophil lactoferrin release, while cross-linking of FcalphaR with MIP8a and anti-mouse IgG could elicit neutrophil lactoferrin release. However, IgA IC-induced lactoferrin release required both extracellular calcium and magnesium, whereas MIP8a-induced release did not require extracellular magnesium and only partially required extracellular calcium. In addition, the time course of IgA IC-induced lactoferrin release was slow. Lactoferrin was not detectable if the incubation time was less than 0.5 h. In contrast, MIP8a-induced lactoferrin release was fast. Lactoferrin could be detected within 5 min of incubation. Therefore, neutrophil lactoferrin release induced by IgA IC differed from that induced by cross-linking of FcalphaR with MIP8a.

Animals↗

PubMed2002

Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance.

BACKGROUND AND AIMS: The natural immunomodulator, lactoferrin, is widespread among various biological fluids and is known to exert an anti-inflammatory effect. However, there has been only one study that examined the mode of action of lactoferrin in reducing intestinal damage. We investigated the therapeutic role of lactoferrin and its effect on the levels of pro-inflammatory and anti-inflammatory cytokines, by using a rat model of dextran sulfate sodium (DSS) induced-colitis. METHODS: Male Sprague-Dawley rats were given distilled drinking water containing 2.5% (wt/vol) synthetic DSS ad libitum. Bovine lactoferrin was given once daily through gavage, starting 3 days before beginning the DSS administration, until death. The whole colon was removed to be examined macroscopically and histologically. Myeloperoxidase activity, and pro-inflammatory and anti-inflammatory cytokines in the colonic tissue were also measured. RESULTS: Dextran sulfate sodium-induced colitis was attenuated by oral administration of lactoferrin in a dose-dependent manner, as reflected by improvement in clinical disease activity index, white blood cell count and hemoglobin concentration, macroscopic and histological scores, and myeloperoxidase activity. Reduced inflammation in response to lactoferrin was correlated with the significant induction of the anti-inflammatory cytokines, interleukin-4 and interleukin-10, and with significant reductions in the pro-inflammatory cytokines, tumor necrosis factor alpha, interleukin-1beta, and interleukin-6. CONCLUSIONS: We concluded that oral administration of lactoferrin exerts a protective effect against the development of colitis in rats via modulation of the immune system and correction of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for inflammatory bowel disease.

Administration, Oral↗

PubMed2001

Inhibitory effect of bovine milk lactoferrin on the interaction between a streptococcal surface protein antigen and human salivary agglutinin.

Human whole saliva induces aggregation of Streptococcus mutans cells via an interaction between a surface protein antigen (PAc) of the organism and salivary agglutinin. Bovine milk inhibits the saliva-induced aggregation of S. mutans. In this study, the milk component that possesses inhibitory activity against this aggregation was isolated and found to be lactoferrin. Surface plasmon resonance analysis indicated that bovine lactoferrin binds more strongly to salivary agglutinin, especially to high molecular mass glycoprotein, which is a component of the agglutinin, than to recombinant PAc. The binding of bovine lactoferrin to salivary agglutinin was thermostable, and the optimal pH for binding was 4.0. To identify the saliva-binding region of bovine lactoferrin, 11 truncated bovine lactoferrin fragments were constructed. A fragment corresponding to the C-terminal half of the lactoferrin molecule had a strong inhibitory effect on the saliva-induced aggregation of S. mutans, whereas a fragment corresponding to the N-terminal half had a weak inhibitory effect. Seven shorter fragments corresponding to lactoferrin residues 473-538 also showed a high ability to inhibit the aggregation of S. mutans. These results suggest that residues 473-538 of bovine lactoferrin are important in the inhibition of saliva-induced aggregation of S. mutans.

Agglutinins↗

PubMed2003

Ultrastructural and cytochemical study of cell wall modification by lactoferrin, lactoferricin and penicillin G against Staphylococcus aureus.

To investigate the effect of lactoferrin or lactoferricin with or without penicillin G, light and transmission electron microscopy were performed on thin sections of two Staphylococcus aureus strains. Lactoferrin affected the ultrastructure of S. aureus and groups of undivided cells were observed after lactoferrin treatment with or without penicillin G. These results suggest that lactoferrin can affect staphylococcal cell separation and therefore prevent dissemination of daughter cells from spreading infection. After treatment with lactoferrin, S. aureus cells were less covered (P<0.05) with wheatgerm agglutinin labelled with gold, thus suggesting that lactoferrin affected the synthesis of peptidoglycan and/or the binding to N-acetyl-beta-D-glucosamine. Lactoferricin with or without penicillin G induced the lysis of many bacteria, formation of mesosomal structures and modifications of cell wall. Lactating female CD-1 mice were infected by intramammary delivery of a penicillin-resistant S. aureus strain and were then randomly assigned to treatments according to a 2 x 2 factorial design. Electron microscopy examination showed that 2 days of systemic treatments with lactoferrin affected the morphology and aggregation of S. aureus. In conclusion, lactoferrin and lactoferricin affect S. aureus morphology which may facilitate its killing by penicillin G.

Animals↗

PubMed1997

Fecal lactoferrin, fecal leukocytes and occult blood in the diagnostic approach to childhood invasive diarrhea.

OBJECTIVE: To compare fecal screening tests in the diagnostic approach to childhood invasive diarrhea. SETTING AND PATIENTS: We assessed 125 consecutive children with acute diarrhea for fecal lactoferrin, fecal leukocytes and occult blood from November, 1995, to June, 1996. RESULTS: Lactoferrin showed a greater overall sensitivity than fecal leukocytes or occult blood for detecting invasive pathogens. Combinations of lactoferrin or fecal leukocytes and of lactoferrin or occult blood or both yielded sensitivities and negative predictive values close to 100%, being superior to all other combinations. All patients with full breast-feeding and mixed feeding had a positive lactoferrin test with a 1:50 dilution used as the cutoff. In controls without diarrhea being exclusively bottle-fed, 3 of 15 (20%) still showed a positive lactoferrin result at the dilution of 1:50. This compared with 15 of 15 (100%) positive results among controls fully breast-fed, 14 of 15 (93%) among controls predominantly breast-fed and 11 of 15 (73%) among control children predominantly bottle-fed. CONCLUSIONS: This study confirms the usefulness of lactoferrin testing as a negative predictor. Breast-feeding lowers the specificity of the test but does not alter the sensitivity. Fecal lactoferrin may be viewed as the screening test of choice to avoid expensive stool cultures in the diagnostic approach to invasive diarrhea.

Child↗

PubMed2002

Lactoferrin in whole gut lavage fluid as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins.

OBJECTIVES: We investigated which neutrophil-derived proteins in whole gut lavage fluid (WGLF) most accurately reflect disease activity in inflammatory bowel disease. METHODS: WGLF was obtained from patients undergoing whole gut lavage as a bowel preparation for colonoscopy. Twenty-seven patients with ulcerative colitis (UC), 23 patients with Crohn's disease (CD), and 35 control subjects were examined. The concentrations of lactoferrin, polymorphonuclear neutrophil elastase (PMN-E), myeloperoxidase, and lysozyme in WGLF were measured by ELISA. For the assessment of stability, WGLF samples were stored at 37 degrees C for various periods. RESULTS: In UC, the concentrations of lactoferrin, myeloperoxidase, and lysozyme in WGLF had good correlations with colonoscopic grading. Zero, 12, five, and 10 of 28 samples from active UC patients showed normal concentrations of lactoferrin, PMN-E, myeloperoxidase, and lysozyme, respectively. In CD, the concentrations of lactoferrin and myeloperoxidase had good correlations with the Crohn's disease activity index. Thirteen and seven of 36 samples from inactive CD patients (Crohn's disease activity index < or = 150) showed high concentrations of lactoferrin and myeloperoxidase, respectively. Most of them (11/13, 6/7) were found to have ulceration by colonoscopy or small bowel x-ray. The ratio of the lactoferrin concentration in the WGLF supernatant to that in total WGLF was highest among these proteins in all disease groups and control subjects. Lactoferrin and myeloperoxidase showed good stability in WGLF, whereas PMN-E and lysozyme did not. CONCLUSION: Lactoferrin is the most suitable of these proteins for use as a neutrophil-derived WGLF marker of intestinal inflammation.

Adult↗

PubMed2003

Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation.

OBJECTIVE: Lactoferrin is a glycoprotein expressed by activated neutrophils. The aim of this study was to determine the sensitivity and specificity of fecal lactoferrin concentrations for inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) versus healthy controls. METHODS: Fresh stool samples were collected from outpatients with ulcerative colitis (UC), Crohn's disease (CD), or IBS. Clinical disease activity for IBD was assessed using a modified Harvey-Bradshaw Activity Index. Fecal lactoferrin concentrations were determined using a polyclonal antibody-based enzyme linked immunoassay. Mean fecal lactoferrin concentrations for each group and sensitivity and specificity of the assay were determined. RESULTS: One hundred-four CD patients, 80 UC patients, 31 IBS patients, and 56 healthy controls were recruited. The mean +/- SE fecal lactoferrin concentration (microg/g fecal weight) was 440 +/- 128 for CD patients, 1125 +/- 498 for UC patients, 1.27 +/- 0.29 for IBS patients, and 1.45 +/- 0.4 for healthy controls. Fecal lactoferrin was 90% specific for identifying inflammation in patients with active IBD. Elevated fecal lactoferrin was 100% specific in ruling out IBS. CONCLUSIONS: Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may prove useful in screening for inflammation in patients presenting with abdominal pain and diarrhea.

Adolescent↗

PubMed1986

Plasma lactoferrin content: differential effect of steroid administration and infective illnesses: lack of effect of ambient temperature at which specimens are collected.

The effect of parenteral hydrocortisone on plasma lactoferrin concentration, neutrophil count and lactoferrin:neutrophil ratio was assessed in 10 volunteer subjects. Administration of a single dose of corticosteroid was followed by a significant rise in the circulating neutrophil count, a significant but proportionately smaller rise in the plasma lactoferrin concentration and a significant fall in the lactoferrin:neutrophil ratio. Acute viral infections were found to be associated with a disproportionately low plasma lactoferrin concentration relative to the circulating neutrophil count. The relatively low lactoferrin concentrations in both these situations could be of significance in regard to the propensity to bacterial infection and superinfection which these 2 groups of subjects display. Compared to patients with viral infection, those suffering from Plasmodium falciparum malaria showed a significantly elevated lactoferrin:neutrophil ratio, although this ratio was not significantly different when malarial patients were compared to normal individuals. These findings suggest that the pathogenesis of relative neutropenia in viral and protozoal illnesses is fundamentally different. Finally, it was found that the temperature at which specimen collection takes place does not appear to be a significant variable determining the plasma lactoferrin concentration.

Acute Disease↗

PubMed1998

Hepatic and extrahepatic clearance of circulating human lactoferrin: an experimental study in rat.

Lactoferrin, unlabelled or 125I-labelled by 2 different methods, was given intravenously to rats. Blood, tissue and liver cell radioactivity was measured. Both of the radiolabelled preparations were eliminated by the liver, and some deposited extrahepatically. One preparation formed large aggregates--here 90% of the hepatic uptake occurred in the Kupffer cells. The other preparation, consisting mostly of protein monomers but also dimers/oligomers/microaggregates, was taken up by hepatocytes (63% of total liver uptake), liver endothelial cells (22%) and Kupffer cells (15%). On a per cell volume basis, lactoferrin uptake was much more efficient by nonparenchymal cells compared to hepatocytes, which explains why immunomorphological staining only revealed lactoferrin in the nonparenchymal liver cells. The study demonstrates that radio-iodination of lactoferrin can affect its properties and handling, which may be important regarding contradictory reports on hepatic lactoferrin uptake. We conclude that both hepatocytes and nonparenchymal liver cells are involved in the blood clearance of lactoferrin, probably to a great extent owing to nonspecific mechanisms. Extrahepatic deposition and exposure (for instance on vessel walls/glomeruli) suggests that lactoferrin can be available to circulating anti-lactoferrin autoantibodies in autoimmune disease.

Animals↗

PubMed1986

The concentration of lactoferrin in tears of normals and of diabetics.

The tear lactoferrin content and the tear secretion rate was determined in 105 normal subjects (age range: 15-93 years) and 21 diabetic patients (age 21-78 years). Tear sampling was performed using glass capillaries and the lactoferrin concentration in tears was tested employing an enzyme-linked immunosorbent assay. Tear secretion rate was measured using standardized Halberg filter paper placed in the inferior fornix for 5 min. The lactoferrin level of normal tears showed a significant inverse correlation with age, the mean value of the 8th decade (0.81 mg/ml) constituting only about half the value of the lactoferrin level found in the 3rd decade (1.48 mg/ml). The tear secretion rate also displayed a significant decrease with age, but no correlation could be demonstrated between the tear secretion rate and lactoferrin concentration. No difference was found in lactoferrin level between men and women. We were not able to demonstrate any correlation between lactoferrin content of tears and the duration of diabetes in the 21 diabetic subjects, and there was no difference between the level of lactoferrin in normal tears compared to the concentration in diabetic tears. No difference was found between the tear secretion rate in normals and in diabetics.

Adolescent↗

PubMed1999

Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates.

Because of the rising incidence of failures in the treatment of oropharyngeal candidosis in the case of severely immunosuppressed patients (mostly human immunodeficiency virus [HIV]-infected patients), there is need for the development of new, more effective agents and/or compounds that support the activity of the common antifungal agents. Since lactoferrin is one of the nonspecific host defense factors present in saliva that exhibit antifungal activity, we studied the antifungal effects of human, bovine, and iron-depleted lactoferrin in combination with fluconazole, amphotericin B, and 5-fluorocytosine in vitro against clinical isolates of Candida species. Distinct antifungal activities of lactoferrin were observed against clinical isolates of Candida. The MICs generally were determined to be in the range of 0.5 to 100 mg. ml(-1). Interestingly, in the combination experiments we observed pronounced cooperative activity against the growth of Candida by using lactoferrin and the three antifungals tested. Only in a limited concentration range was minor antagonism detected. The use of lactoferrin and fluconazole appeared to be the most successful combination. Significant reductions in the minimal effective concentrations of fluconazole were found when it was combined with a relatively low lactoferrin concentration (1 mg/ml). Such combinations still resulted in complete growth inhibition, while synergy of up to 50% against several Candida species was observed. It is concluded that the combined use of lactoferrin and antifungals against severe infections with Candida is an attractive therapeutic option. Since fluconazole-resistant Candida species have frequently been reported, especially in HIV-infected patients, the addition of lactoferrin to the existing fluconazole therapy could postpone the occurrence of species resistance against fluconazole. Clinical studies to further elucidate the potential utility of this combination therapy have been initiated.

Amphotericin B↗

PubMed1996

Distribution of lactoferrin and 60/65 kDa heat shock protein in normal and inflamed human intestine and liver.

Immunisation against the mycobacterial heat shock protein (hsp-65) has been proposed to lead to production of autoantibodies against human lactoferrin. Such antibodies occur in ulcerative colitis and in primary sclerosing cholangitis. This study analysed the distribution of hsp-65 and lactoferrin in biopsy specimens from patients with inflammatory bowel disease and primary sclerosing cholangitis and studied whether immunisation against mycobacterial hsp-65 resulted in production of antilactoferrin antibodies and vice versa. Polyclonal rabbit antihuman lactoferrin and monoclonal mouse anti-hsp-65 (ML30) were used for immunohistochemistry on biopsy specimens from patients with inflammatory bowel disease and primary sclerosing cholangitis. Rats were immunised against human lactoferrin and mycobacterial hsp-65 respectively. Antibody measurements were done by enzyme immunosorbent assays. It was found that lactoferrin and hsp-60/65 were not codistributed. Lactoferrin was found on vascular endothelium and in nonparenchymal liver cells both in inflamed and uninflamed tissues, but only in the hepatocytes of inflamed liver. ML30 reactivity was not inhibited by antilactoferrin antibodies. Rat anti-hsp-65 serum had no detectable antilactoferrin antibodies. In conclusion, antilactoferrin antibodies probably do not arise by immunisation against mycobacterial hsp-65. Both nonparenchymal cells and hepatocytes probably participate in clearance of lactoferrin. Endothelial exposure of lactoferrin may have pathogenic implications in diseases with antilactoferrin autoantibodies.

Animals↗

PubMed1983

Lactoferrin-deficient neutrophil polymorphonuclear leucocytes in leukaemias: a semiquantitative and ultrastructural cytochemical study.

Semiquantitative analysis of lactoferrin deficiency in neutrophil polymorphonuclear leucocytes in various haematological and non-haematological disease was carried out by scoring polymorphonuclear leucocytes stained for lactoferrin by the immunoperoxidase method. The staining patterns for lactoferrin were classified into four types (0-III) based on the intensity of reaction, and the sum of the ratings of 100 polymorphonuclear leucocytes was considered as "lactoferrin score" with a possible range of 0-300. As a result, significantly low lactoferrin-scores were frequently observed in acute leukaemias and the acute phase of chronic leukaemias. Of 35 cases with leukaemias, lactoferrin-negative polymorphonuclear leucocytes (type 0) were observed in the following cases: eight cases of acute myelogenous leukaemia (8/14), a case of chronic myelogenous leukaemia (1/10) in blast crisis, one of acute promyelocytic leukaemia (1/1), one of acute monocytic leukaemia (1/2), and a case of chronic myelomonocytic leukaemia (1/2) in a transitional phase to an acute myelomonocytic leukaemia. In two cases of acute myelogenous leukaemia, in which the majority of polymorphonuclear leucocytes were negative for lactoferrin, ultrastructural cytochemical study revealed total lack of specific granules in these polymorphonuclear leucocytes. This suggests that lactoferrin is localised in the specific granules of neutrophils as has been postulated previously by others.

Adolescent↗

PubMed1981

Ultrastructural localisation of lactoferrin and glycoprotein in human bronchial glands.

The distribution of lactoferrin and glycoprotein in human bronchial glands has been studied by electron microscopy using an immunoperoxidase method to stain the former and a periodic acid-chromic acid-silver methenamine sequence for the latter, each applied to ultrathin Epon sections. The distribution of lactoferrin corresponds to that of lysozyme. Lactoferrin and lysozyme are both confined to serous acini where the granules show a variable pattern of staining. Some serous granules are filled uniformly with lactoferrin, some lack lactoferrin in a small central core or a thin peripheral rim, and some are completely devoid of lactoferrin. Glycoprotein is present in all mucous granules but only certain serous granules. The latter may be filled uniformly with glycoprotein or glycoprotein may form a thin peripheral coat about centrally located lactoferrin and lysozyme. An electron-dense central core found in some serous granules contains neither glycoprotein, lactoferrin, nor lysozyme.

Bronchi↗

PubMed2002

Detection of exon polymorphisms in the human lactoferrin gene.

We previously demonstrated that lactoferrin gene polymorphisms occur in cancer cells of patients with leukemia and breast cancer. In this study, we established a non-radioactive polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis, one of the most sensitive and simplest methods to detect polymorphisms and mutations of the human lactoferrin gene. We optimized the PCR conditions for nine different DNA templates and 16 pairs of exon primers for SSCP analysis. The DNA templates used in the analyses were prepared from a cosmid clone (CT6-1) that contains the human lactoferrin gene, human placental tissue, leukocytes from 10 normal volunteers, leukemic cells of two patients, and previously established three breast and two leukemic cell lines. With the appropriate exon-primer sets, PCR products from exon I to exon 16 of the lactoferrin gene were generated from the DNA templates and analyzed by SSCP. Compared with the homogenous cloned DNA, lactoferrin gene polymorphisms were detected within exons 2, 5, 7, 9, 13, 14, and 15 of the normal placental and leukocyte DNA. In addition, abnormal migration patterns of the lactoferrin gene in cancer cells were detected in exons 4, 5, 13, 14, and 15. The PCR-SSCP band migration patterns can be attributed either to gene polymorphism in normal cells or to DNA mutations in cancer cells and the employed method cannot distinguish between them. Nonetheless, the present analysis suggests that genetic polymorphisms of the lactoferrin gene exist in selected exons and additional mutations of the lactoferrin gene do occur in the cancer cells.

Breast Neoplasms↗

PubMed2006

Lactoferrin promotes collagen gel contractile activity of fibroblasts mediated by lipoprotein receptors.

Lactoferrin is an iron-binding glycoprotein that belongs to the transferrin family. Recent studies in vitro and in vivo suggest that lactoferrin is a potential therapeutic agent for wound healing. We have shown that both bovine and human lactoferrin enhance the collagen gel contractile activity of WI-38 human fibroblasts. The collagen gel contraction is considered as an in vitro model for reorganization of the collagen matrix during the wound healing process. The elevation of collagen gel contractile activity induced by lactoferrin was accompanied by activation of extracellular-regulated kinase (ERK) 1/2 and myosin light chain kinase (MLCK), and subsequent elevation of myosin light chain (MLC) phosphorylation. The effects of lactoferrin on collagen gel contraction and the activation of the signaling pathway were dependent on the expression of low-density lipoprotein receptor - related protein (LRP) - 1 in the fibroblasts. LRP-1 is known as an endocytosis receptor and is involved in the cellular uptake of diverse ligands, including lactoferrin. In addition, LRP-1 acts as a signaling lactoferrin receptor in mammalian cells by converting the lactoferrin-binding signal into the activation of the intracellular signaling pathway. This property was found to be independent of the endocytic function of LRP-1, as seen in osteoblast-like cells.

Animals↗