Increased levels of lactoferrin in synovial fluid but not in serum from patients with rheumatoid arthritis

Caccavo, Domenico; Sebastiani, Gian Domenico; Monaco, Cristina Di; Guido, Francesco; Gargiulo, Mauro; Ferri, Gm; Bonomo, Lorenzo; Afeltra, Antonella

doi:10.1007/s005990050059

Cited by 40 publications

(30 citation statements)

References 31 publications

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“…Cultures were grown to 80% confluence and passaged. To examine the effects of LF on terminal differentiation, the hADSCs were cultured in an osteogenic medium [growth culture medium supplemented with 10 −8 M dexamethasone (Sigma), 50 μg/ml ascorbic acid (Sigma) and 5 mM β-glycerol phosphate (Sigma)] at an initial density of 1×10 4 cells/cm 2 with 0, 10, 50 or 100 μg/ml LF (Fonterra), based on a report that the local concentration of LF is 1-100 μg/ml during inflammation [7]. The medium was changed every four days during osteogenic differentiation.…”

Section: Methodsmentioning

confidence: 99%

“…It is produced by many exocrine glands and consequently is widely distributed in body fluids, including milk, saliva, tears, bile and pancreatic fluid [6]. The serum level of LF in healthy subjects ranges from 2 to 7 μg/ml and is predominantly neutrophil derived, but in the presence of inflammation and sepsis, local concentrations may be much higher (1-100 μg/ml) [7]. LF participates in host defences due to its antibacterial and antiviral activities [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Effect of lactoferrin on osteogenic differentiation of human adipose stem cells

Ying

Cheng

Wang

et al. 2011

International Orthopaedics (SICOT)

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Purpose Many in vitro studies of the analysis of the lactoferrin (LF) effect on cells have been reported. However, no study has yet investigated the effect of LF on osteogenic differentiation of human adipose-derived stem cells (hADSCs). The aim of this study was to evaluate the effect of LF on osteogenic differentiation of human adipose stem cells.Methods The hADSCs were cultured in an osteogenic medium with 0, 10, 50 and 100 μg/ml LF, respectively. hADSC proliferation was analysed by Cell Counting Kit-8 (CCK-8) assay, and cell osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, von Kossa staining and real-time polymerase chain reaction (RT-PCR). Results Cell proliferation was significantly increased by LF in a dose-dependent manner from days 4 to 14. Cells cultured with 100 μg/ml LF presented a higher activity compared with the control. The deposition of calcium was increased after the addition of LF. The mRNA expression of type I collagen (COL-I), ALP, osteocalcin (OCN) and RUNX2 increased markedly as a result of LF treatment. Conclusions We have shown for the first time that LF could promote the proliferation and osteogenic differentiation of hADSCs, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of lactoferrin on osteogenic differentiation of human adipose stem cells

Ying

Cheng

Wang

et al. 2011

International Orthopaedics (SICOT)

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“…[7][8][9] Serum levels of lactoferrin are predominantly neutrophil-derived and in healthy subjects range from 2 µg/ml to 7 µg/ml, but during inflammation its local concentrations are much higher. 10 Lactoferrin acts as an iron-chelator, which may contribute to its antimicrobial activity, 11 but it also has effects on cell growth and differentiation, 12 embryonic development, 13 myelopoiesis, 14 endothelial cell adhesion, 15 cytokine 16,17 and chemokine 18 production, regulation of the immune system, 19 and modulation of the inflammatory response. 20 We investigated the effects and mechanism of action of lactoferrin in bone cells in vitro and in a local injection model in vivo.…”

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confidence: 99%

Lactoferrin - A Novel Bone Growth Factor

Naot¹,

Grey²,

Reid³

et al. 2005

Clinical Medicine & Research

148

101

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Lactoferrin is an iron-binding glycoprotein that belongs to the transferrin family. It is present in breast milk, in epithelial secretions, and in the secondary granules of neutrophils. In healthy subjects lactoferrin circulates at concentrations of 2-7 x 10 -6 g/ml. Lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. Recently, we have shown that lactoferrin can also promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and also acts as a survival factor inhibiting apoptosis induced by serum withdrawal. Lactoferrin also affects osteoclast formation and, in murine bone marrow culture, lactoferrin potently inhibits osteoclastogenesis. In vivo, local injection of lactoferrin above the hemicalvaria of adult mice results in substantial increases in the dynamic histomorphometric indices of bone formation and bone area.The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through LRP1, a member of the family of low-density lipoprotein receptor-related proteins that are primarily known as endocytic receptors. Using confocal laser scanning microscopy, we demonstrated that fluorescently labeled lactoferrin is endocytosed and can be visualized in the cytoplasm of primary osteoblastic cells. Lactoferrin also induces activation of p42/44 MAPK signaling in primary osteoblasts, but the two pathways seem to operate independently as activation of MAPK signaling, but not endocytosis, is necessary for the mitogenic effect of lactoferrin. We conclude that lactoferrin may have a physiological role in bone growth and healing, and a potential therapeutic role as an anabolic factor in osteoporosis.

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“…This is a serious problem and such patients may die by suffocation with their own sputum. It is well known that LF is secreted by neutrophils that migrate at inflammation sites, like tracheo-bronchia in bronchitis or synovial fluid in arthritis (4). The injection of hLF may create a condition that mimics inflammation, and may attract healing functions by some unknown mechanism.…”

Section: Effect Of Human and Bovine Lactoferrin On Accumulation Of Asmentioning

confidence: 99%

Intraperitoneal injection of lactoferrin ameliorates severe albumin extravasation and neutrophilia in LPS-induced inflammation in neonatal rats

Yajima

Kuwata

2005

Biomed. Res.

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Lactoferrin (LF) plays various anti-inflammatory roles in inflammation experimentally induced by lipopolysaccharides (LPS). But the effects of LF on albumin extravasation and neutrophilia have not been elucidated. We aimed to study the effects of LF on albumin extravasation, neutrophilia and/or on other symptoms in inflammation caused by LPS in rats. Human lactoferrin (hLF) was injected (10 mg/100 mL in PBS) 18 h, or 15 min prior to, or 60 min after intraperitoneal injection of LPS in 13 days old Sprague Dawley rats. Prophylactic injection of hLF significantly ameliorated albumin extravasation in ascitic fluid at 5 h and neutrophilia in the blood at 24 h after LPS injection, but the after-injection of hLF did not. Interestingly, an injection of rat anti-TNFα IgG 15 min prior to LPS injection did not ameliorate albumin extravasation. Prophylactic injection of hLF significantly ameliorated other symptoms like mortality, and the decrease of phagocytotic activity of peritoneal polymorpho-nuclear leukocytes (PMNL), but did not ameliorate the decrease of platelets in the plasma. These findings suggest that hLF may be available as a medical treatment prior to surgery for prophylaxis of side effects like albumin extravasation or neutrophilia.Lactoferrin (LF) has diverse homeostatic activities in relation to anti-bacterial, anti-viral and anti-inflammatory immunological activities (12, 13). It is reported that prophylactic treatment by injection of human lactoferrin (hLF) reduced lipopolysaccharide (LPS)-induced TNFα production and the death rate in mice (15). In general, intraperitoneal injection of LPS (LPS-ip-injection), a cell wall component of gram-negative bacteria, induces severe septic like inflammation with production of TNFα and neutrophilia (6) in the plasma of experimental animals. In clinical patients suffering from spontaneous bacterial peritonitis, ascites are frequently found. More than 92% of these patients have monomicrobial infections with aerobic gram-negative bacilli that contain LPS in their cell walls (7). However, it is not known whether a prophylactic injection of hLF has homeostatic effects on albumin extravasation or neutrophilia after LPS-ip-injection. In the present study, we showed gross albumin accumulation in ascitic fluid 5 h after LPS injection in neonatal rats. Using this neonatal model, we examined whether LF had the ability to ameliorate gross albumin extravasations in the peritoneal cavity that followed LPS injection. We also examined changes in blood components like platelets, and what does relate to rat anti-TNFα IgG injected at the same site just prior to LPS injection. We also examined whether hLF had prophylactic effects on the decrease of the phagocytotic activity after LPS injection.

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Increased levels of lactoferrin in synovial fluid but not in serum from patients with rheumatoid arthritis

Cited by 40 publications

References 31 publications

Effect of lactoferrin on osteogenic differentiation of human adipose stem cells

Effect of lactoferrin on osteogenic differentiation of human adipose stem cells

Lactoferrin - A Novel Bone Growth Factor

Intraperitoneal injection of lactoferrin ameliorates severe albumin extravasation and neutrophilia in LPS-induced inflammation in neonatal rats

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