Figure 6 shows a possible scheme on how LF might interfere with SARS-CoV-2 binding. Would you like email updates of new search results? Taking lactoferrin supplements can protect against microbial infection, an inflammatory reaction, and skin issues. J Am Chem Soc. doi: 10.3390/ijms18040870, 12. The treatment of black stain associated with of iron metabolism disorders with lactoferrin: a litterature search and two case studies. (2011) 16:70414. (2018) 18:13447. Iron toxicity is associated with diarrhea, reduced feed intake, and weight gain. So it does potentially have benefit, but not that. Sham RL, Phatak PD, West C, Lee P, Andrews C, Beutler E. Blood Cells Mol Dis. (2018) 92:e0193317. How drugs get into cells: tested and testable predictions to help discriminate between transporter-mediated uptake and lipoidal bilayer diffusion. J Pediatr. Carro E, Bartolom F, Bermejo-Pareja F, Villarejo-Galende A, Molina JA, Ortiz P, et al. Intestinal inflammation is associated with, for example, some bacterial infections and, in people with inflammatory bowel disease (IBD), it is associated with disease activity and severity. (2009) 2:2. doi: 10.1186/1755-8794-2-2, 29. HSPGs themselves are not sufficient for SARS-CoV entry. Aerosolized bovine lactoferrin counteracts infection, inflammation and iron dysbalance in a cystic fibrosis mouse model of Pseudomonas aeruginosa chronic lung infection. Urban CF, Ermert D, Schmid M, Abu-Abed U, Goosmann C, Nacken W, et al. Nat Rev Drug Discov. doi: 10.1371/journal.ppat.1000949, 31. (2009) 81:40929. Drug Disc Today. (2020) 2:296303. 2007 Jan;81(1):195-204. doi: 10.1189/jlb.0606405. Dobson PD, Kell DB. (2017) 46:190200. doi: 10.1038/s41589-020-0483-3, 125. Autoimmun Rev. Yang J, Li H, Hu S, Zhou Y. ACE2 correlated with immune infiltration serves as a prognostic biomarker in endometrial carcinoma and renal papillary cell carcinoma: implication for COVID-19. Clin Vaccine Immunol. Nat Rev Rheumatol. doi: 10.1016/j.micpath.2018.12.008, 86. Similarly LF supplements may play an important role to counteract bacterial processes. Strategies for manipulating metabolic fluxes in biotechnology. 4. Importantly, LF also binds to heparan sulfate proteoglycans (HSPGs), which are cell-surface and extracellular matrix macromolecules that are composed of a core protein decorated with covalently linked glycosaminoglycan (GAG) chains (86, 87, 98, 99). Biochem Cell Biol. (1999) 124:3217. Neuron. Patel P, Shah J. Though a natural component of cows' and human mothers' milk, lactoferrin is found throughout the human body.22,23 If you already have one of these conditions, phlebotomy may slow the progression of the disease. (1974) 365:3117. doi: 10.1016/j.neuron.2007.08.008, 90. doi: 10.1182/blood-2018-11-844530, 138. 176. Lactoferrin (LF) or lactotransferrin has recently come under the spotlight, particularly with regards to the new coronavirus pandemic that started in 2019 (COVID-19). Liao H, Liu S, Wang H, Su H, Liu Z. Kell DB, Knowles JD. LF is thought to exert its main biological activities following interaction with receptors on target cells. 2, No. 3. doi: 10.1016/j.prosdent.2013.12.028, 58. doi: 10.1111/jth.14851, 180. Sangermano R, Pernarella S, Straker M, Lepanto MS, Rosa L, Cutone A, et al. Kanekiyo T, Cirrito JR, Liu CC, Shinohara M, Li J, Schuler DR, et al. We discuss (1) discovery and structure of LF; (2) LF membrane receptors and some of the bacteria, their products and viruses that might also bind to these receptors, (3) including how acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (causing COVID-19) may interact with host cells (see Figure 6 and Conclusion for a detailed discussion); (4) and how LF assists with host immunity. Kell DB, Pretorius E. To what extent are the terminal stages of sepsis, septic shock, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome actually driven by a prion/amyloid form of fibrin? doi: 10.1007/3-540-29916-5_6, 47. (2019) 13:315. BMC Microbiol. (2017) 95:5763. Int Dairy J. 1979 Oct-Dec;24(4):193-206. Delgado-Rizo V, Martnez-Guzmn MA, Iiguez-Gutierrez L, Garca-Orozco A, Alvarado-Navarro A, Fafutis-Morris M. Neutrophil extracellular traps and its implications in inflammation: an overview. HHS Vulnerability Disclosure, Help Furmanski P, Li ZP, Fortuna MB, Swamy CV, Das MR. It has important immunological properties, and is both antibacterial and antiviral. (2015) 7:133977. and transmitted securely. Lactoferrin is a multi-purpose protein from the transferrin family. Okubo K, Kamiya M, Urano Y, Nishi H, Herter JM, Mayadas T, et al. See Figure 3. Kell DB, Pretorius E. On the translocation of bacteria and their lipopolysaccharides between blood and peripheral locations in chronic, inflammatory diseases: the central roles of LPS and LPS-induced cell death. Biol Pharm Bull. Clin Transl Imaging. doi: 10.1139/o2012-016, 11. Is hereditary hemochromatosis a balanced polymorphism: an analysis of family size among hemochromatosis heterozygotes. As well as binding it directly from the environment, bacterial siderophores can obtain iron by removing it from transferrin, lactoferrin, or ferritin (32). Bookshelf Rosa L, Cutone A, Lepanto MS, Paesano R, Valenti P. Lactoferrin: a natural glycoprotein involved in iron and inflammatory homeostasis. As part of the host's inflammatory response, leucocytes, including neutrophils, release LF from their granules, where it is normally stored. The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, HIV infections. and transmitted securely. (2003) 50:12331. Front Pharmacol. SARS-CoV bound to HSPGs then rolls onto the cell membrane and scans for specific entry receptors, which leads to subsequent cell entry (99). Lactoferrin, a minor fraction of whey, appears to have a wide variety of uses in biological systems and is considered a first line of immune defense in the human body. Dreyfuss JL, Regatieri CV, Jarrouge TR, Cavalheiro RP, Sampaio LO, Nader HB. (2013) 75:15964. (2019) 170:e37381. doi: 10.1002/dmrr.3319. Science. In adults of many species, lactoferrin is expressed and secreted by glandular epithelial cells ( 27, 32 ). PLoS ONE. Another recent review (196) has also highlighted the potential utility of lactoferrin as an antiviral. Because of increased awareness and earlier diagnosis, the end-organ damage secondary to iron overload is not often seen in clinical practice. Trends Pharmacol Sci. HSPGs provide the first anchoring sites on the host cell surface, and help the virus make primary contact with these cells (99, 162). doi: 10.1177/0890334415592402, 36. Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose. (1998) 30:105562. LF has strong antiviral activity against a broad spectrum of both naked and enveloped DNA and RNA viruses (99, 149151). (2014) 337:58195. A common initial presentation is an asymptomatic patient with mildly elevated liver enzymes who is subsequently found to have elevated serum ferritin and transferrin saturation. Epub 2006 Feb 17. Lactoferrin is one of the components of the immune system and is part of the non-specific immune response of the mucous Membranes. LF may therefore be an excellent supplement to take, not only as a contribution to prevention but perhaps as a therapy in the event COVID-19 is diagnosed. An official website of the United States government. A primary bacterial defense against siderocalin involves the production of stealth siderophores. (2012) 90:24551. (2011) 3:a004952. (2019) 80(Suppl. doi: 10.1139/o01-212, 25. Biochem Cell Biol. Ishikado A, Imanaka H, Takeuchi T, Harada E, Makino T. Liposomalization of lactoferrin enhanced it's anti-inflammatory effects via oral administration. Posey JE, Gherardini FC. When erythrocytes lyse and hemoglobin or haem is released into the circulation, their hemoglobin is captured by haptoglobin, and haem by hemopexin (30). Circulating iron is rapidly bound by transferrin (28, 29). 2):e12949. (2020). Fleming RE, Britton RS, Waheed A, Sly WS, Bacon BR. (2018) 2:198207. Lactoferrin50 years on. 2001 Summer;14(3):196-208; quiz 220-2. Due to its similarities to transferrin, which is the main iron transporting molecule in serum (22, 23), -LF possesses iron binding capabilities (24, 25), and it can chelate two ferric irons (Fe3+) (26). Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS). The relatively lower risk for COVID-19 found in individuals with blood group O may be linked to a lower serum iron status in these individuals. The body can produce substances such as lactoferrin that binds free iron, making it unavailable for bacterial growth and preventing bacterial infection. Togawa J, Nagase H, Tanaka K, Inamori M, Umezawa T, Nakajima A, et al. Carvalho CAM, Casseb SMM, Goncalves RB, Silva EVP, Gomes AMO, Vasconcelos PFC. They are present in capsule or powder form. doi: 10.1126/science.1164860, 23. (2008) 31:16058. Front Immunol. doi: 10.1099/jgv.0.000849, 152. Int J Biochem Cell Biol. Tfr2 results from the transcription of all exons, and is prevalently and highly expressed in hepatocytes and erythroid cell lines. doi: 10.1515/CCLM.2003.021, 45. Figure 4 shows how bacteria acquire iron through receptor-mediated recognition of transferrin, hemopexin, hemoglobin, or hemoglobin-haptoglobin complexes and also LF (30). Crit Rev Food Sci Nutr. doi: 10.1113/expphysiol.2006.034876, 129. Cole AM. (2018) 561:1226. Phlebotomy is the mainstay of treatment and can help improve heart function, reduce abnormal skin pigmentation, and lessen the risk of liver complications. Many COVID-19 patients develop acute respiratory distress syndrome (ARDS), which leads to pulmonary edema and lung failure, and have liver, heart, and kidney damages. In addition to DNA and histones, NET fibers contain extranuclear proteins and proteins such as elastase, myeloperoxidase (MPO), and LF (141). Human milk components modulate Toll-like receptor-mediated inflammation. Autosomal dominant hereditary hemochromatosis associated with a novel ferroportin mutation and unique clinical features. Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins. (2020). Lippi G, Plebani M, Henry BM. Genetic testing for the hereditary hemochromatosis genes should be offered after 18 years of age to first-degree relatives of patients with the condition. (2004) 64:638. Effect of lactoferrin on taste and smell abnormalities induced by chemotherapy: a proteome analysis. Nutrients. (2020). (1980) 96:3804. Human milk composition: nutrients and bioactive factors. (2020). doi: 10.2147/CCID.S228153. Curr Top Microbiol Immunol. (2017) 16:116073. Futosi K, Fodor S, Mcsai A. Neutrophil cell surface receptors and their intracellular signal transduction pathways. The physiology of lactoferrin. doi: 10.1016/S1095-6433(99)00122-1, 126. J Inflamm. Biometals. Crit Rev Biochem Mol Biol. Pulsatile stimulation determines timing and specificity of NF-kappaB-dependent transcription. Adapted from Jorch and Kubes (142) and Law and Gray (143). Integr Biol. Iron regulatory proteins 1 and 2 in human monocytes, macrophages and duodenum: expression and regulation in hereditary hemochromatosis and iron deficiency. (1993) 28:1306. (2019) 59:58096. (2018) 107:715. Valenti P, Rosa L, Capobianco D, Lepanto MS, Schiavi E, Cutone A, et al. The test may be ordered to distinguish between IBD and non . 14. doi: 10.1016/S0968-0004(03)00031-8, 163. Nutrients. Adv Nutr. doi: 10.1016/j.cca.2020.03.022, 175. Serum amyloid A and inflammation in diabetic kidney disease and podocytes. Seong K-J, Lee H-G, Kook MS, Ko H-M, Jung J-Y, Kim W-J. Peroni DG. Iron in human milk. J Virol. Clin Lab Sci. Inhibition of the TIRAP-c-Jun interaction as a therapeutic strategy for AP1-mediated inflammatory responses. (2011) 6:e23710. (1988) 55:118993. Lactoferrin is safe in amounts consumed in food. Skaar EP. Uptake of lactoferrin by mononuclear phagocytes inhibits their ability to form hydroxyl radical and protects them from membrane autoperoxidation. However, more than 90% of LF in human milk is in the form of apolactoferrin (160), which competes with siderophilic bacteria for ferric iron, and disrupts the proliferation of these microbial and other pathogens. (1998) 66:48691. When it is iron-rich it is referred to hololactoferrin and when iron-free apolactoferrin (18). doi: 10.1128/CVI.00636-12, 174. (2019) 11:E2350. Host innate immune functions are supported by the circulating protein, siderocalin, also known as Neutrophil gelatinase-associated lipocalin (NGAL), lipocalin2 or Lcn2 as it inhibits siderophore-mediated iron acquisition and release (30). White KN, Conesa C, Snchez L, Amini M, Farnaud S, Lorvoralak C, et al. doi: 10.1096/fba.2020-00015, 9. Amersham) and plasma lactoferrin by an ELISA [5]. LF acts as an important element in host defense mechanisms by binding to these receptors, but also binding to HSPG on cells, since these are locations where binding to bacteria and their cell wall products as well as viruses occur. doi: 10.1128/IAI.00545-15, 113. Liver transplantation may be considered in select patients. PLoS Pathog. F. Study on the effects of an oral lactobacilli and lactoferrin complex in women with intermediate vaginal microbiota. Cellular uptake and release of intact lactoferrin and its derivatives in an intestinal enterocyte model of Caco-2 cells. (2018) 44: 22438. (2005) 6:2. doi: 10.1186/1471-2172-6-2, 136. Med Hypotheses. Lactoferrin is a very important bioactive molecule that provides iron to cells that need it and limits it to those in excess. See permissionsforcopyrightquestions and/or permission requests. These multiple receptors arguably underpin the substantial and widespread effects that LF can induce, since only when multiple targets are hit simultaneously can one normally have major effects (103, 104). Transferrin receptor, lactoferrin receptor, hemophore (Hp), hemophore receptor, and hemopexin. doi: 10.1039/C8FO00813B, 53. Microb Pathog. doi: 10.1007/s12185-017-2366-2, 28. New sensitive method for the measurement of lysozyme and lactoferrin for the assessment of innate mucosal immunity. (2014) 88:1322130. (2013) 34:95107. (2011) 6:e19433. (2007) 56:6678. Trends Biochem Sci. (1990) 344:7847. As a nutraceutical, the bioavailability of LF would clearly be an important consideration in its use for the prevention or treatment of COVID-19. Early diagnosis of mild cognitive impairment and Alzheimer's disease based on salivary lactoferrin. Here, circulating serum ferroxidase ceruloplasmin is of importance, as LF can bind to ceruloplasmin, such that a direct transfer of ferric iron between the two proteins is possible (31). Stealth siderophores are modified in such a way as to prevent siderocalin binding. doi: 10.1017/S0954422419000301. (2018) 10:1228. doi: 10.3390/nu10091228, 35. (2017) 18:E870. The role of modeling in systems biology. Koshi R, Kotani K, Ohtsu M, Yoshinuma N, Sugano N. Application of lactoferrin and 1-antitrypsin in gingival retention fluid to diagnosis of periodontal disease. (2017) 106:158. doi: 10.1038/s41586-018-0433-3, 107. Simplified platelet signaling and receptor activation during disease with main dysregulated molecules thrombin, fibrin(ogen), von Willebrand Factor (vWF) interleukins (IL) like IL-1, IL-1, and IL17A and cytokines like TNF-. (2017) 17:71421. (2019) 25:105561. HHS Vulnerability Disclosure, Help Int Immunopharmacol. The liver, pancreas, joints, heart, skin, and pituitary gland are the most commonly involved organs. (1997) 274:22236. Thromb Res. Careers. It is the most common inherited disorder among people of northern European ancestry. We summarize the layout of this paper in Figure 1. J Microbiol Immunol Infect. Karav S, German JB, Rouqui C, Le Parc A, Barile D. Studying lactoferrin N-glycosylation. doi: 10.1038/s41440-020-0455-8. doi: 10.1055/s-0040-1708827, 79. Antimicrob Agents Chemother. Nature. doi: 10.1113/expphysiol.2003.026633, 132. Biol Pharm Bull. Comp Biochem Physiol A Mol Integr Physiol. Wu D, Yang XO. Colostrum, the first milk made after a baby is born, is higher in lactoferrin. Naskalska A, Dabrowska A, Szczepanski A, Milewska A, Jasik KP, Pyrc K. Membrane protein of human coronavirus NL63 is responsible for interaction with the adhesion receptor. Dis Markers. LF may also serve as an intrinsic inhibitor of NETs release into the circulation, and may therefore be central in controlling NETs release (1). 168. Bovine LF contains 689 amino acids (13). Wang B, Timilsena YP, Blanch E, Adhikari B. Lactoferrin: structure, function, denaturation and digestion. Mol Microbiol. But I'm not sure you'd want to use whey. (2007) 72:8505. doi: 10.1007/s40336-016-0211-x, 145. doi: 10.1039/C7FO01559C, 42. Nat Rev Immunol. Blood. Macrophage CD14 impacts immune defenses against influenza virus in allergic hosts. doi: 10.1016/S0304-4165(01)00178-7, 166. (2005) 62:256075. Lipopolysaccharide stimulates platelet secretion and potentiates platelet aggregation via TLR4/MyD88 and the cGMP-dependent protein kinase pathway. J Thromb Haemost. This may indicate a bacterial infection or inflammatory bowel disease (IBD). Clin Exp Rheumatol. Exp Physiol. doi: 10.1158/1078-0432.CCR-19-0081, 84. There are also three different isoforms: LF- is the iron-binding isoform, while LF- and LF-g both have ribonuclease activity but do not bind iron (11, 17). Science. Anderson BF, Baker HM, Norris GE, Rumball SV, Baker EN. Table 3. (1992) 1121:1306. (2020) 18:109499. One of the most well-known characteristics of LF is that it is antibacterial (19, 144148), antiviral (99, 149151), antifungal (152154), anti-inflammatory (26), and anti-carcinogenic (155). Cornish-Bowden A, Hofmeyr J-HS, Crdenas ML. doi: 10.1101/cshperspect.a004952, 87. Cochrane Database Syst Rev. Neutrophil extracellular traps kill bacteria. FASEB Bioadv. doi: 10.1111/j.1462-5822.2010.01529.x, 157. doi: 10.1016/j.jpeds.2016.02.071, 162. Accessibility Kamemori N, Takeuchi T, Sugiyama A, Miyabayashi M, Kitagawa H, Shimizu H, et al. Rev Ig Bacteriol Virusol Parazitol Epidemiol Pneumoftiziol Bacteriol Virusol Parazitol Epidemiol. Multiple molecular forms of human lactoferrin. 177. Ganz T. Iron and infection. Gao CH, Dong HL, Tai L, Gao XM. Zhang G, Zhang J, Wang B, Zhu X, Wang Q, Qiu S. Analysis of clinical characteristics and laboratory findings of 95 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a retrospective analysis. doi: 10.1084/jem.170.2.415, 18. Biomed J. Kimoto Y, Nishinohara M, Sugiyama A, Haruna A, Takeuchi T. Protective effect of lactoferrin on cisplatin-induced nephrotoxicity in rats. Heparan sulfate proteoglycans: structure, protein interactions and cell signaling. Seo YD, Jiang X, Sullivan KM, Jalikis FG, Smythe KS, Abbasi A, et al. Cell Death Dis. doi: 10.1139/bcb-2016-0039, 69. Annu Rev Biochem. 1995 Jun 1;308 ( Pt 2)(Pt 2):391-7. doi: 10.1042/bj3080391. doi: 10.1007/3-540-29916-5_8, 44. Moore SA, Anderson BF, Groom CR, Haridas M, Baker EN. Am J Physiol Heart Circ Physiol. Entry of human coronavirus NL63 into the cell. Phosphorylation of relevant substrates (e.g., enzymes, microtubules, histones, and transcription factors) plays a crucial role in determining the host's cellular response (109). Figure 1 shows the decline in serum ferritin during phlebotomy in the patient with heredi tary hemochromatosis. Hemochromatosis is a hereditary condition that causes the body to accumulate an excess of iron. Nature. Lancet. Drug Disc Today. Frankel AD, Pabo CO. Cellular uptake of the tat protein from human immunodeficiency virus. Curr Opin Microbiol. De Filippo K, Rankin SM. Diagram created with BioRender (https://biorender.com/). doi: 10.1139/o01-214, 49. Copyright 2020 Kell, Heyden and Pretorius. (2012) 130:e738. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity. Immunol Invest. Genetic testing for the C282Y and H63D mutations of the. 1979. Clipboard, Search History, and several other advanced features are temporarily unavailable. Tse GM, To KF, Chan PK, Lo AW, Ng KC, Wu A, et al. (2020) 318:H108490. [Epub ahead of print]. See Table 1 for selected references. Lactoferrin level in breast milk: a study of 248 samples from eight regions in China. Currently, there is also a renewed interest in ACE2 and HSPG blocking, as discussed in the introduction (58). Available online at: https://www.clinexprheumatol.org/abstract.asp?a=10879, 139. (1971) 20:4205. (2000) 288:16513. Infect Immun. (2020) 46:30219. Nat Rev Drug Disc. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. Lactoferrin is a prominent component of the granules of polymorphonuclear leukocytes. Please enable it to take advantage of the complete set of features! doi: 10.1080/10409238.2017.1293606, 147. Platelets at the crossroads of thrombosis, inflammation and haemolysis. (2017) 8:81. doi: 10.3389/fimmu.2017.00081, 50. In addition, iron overload can cause: Arthritis (joint damage). (2002) 80:16. (2018) 41:6387. LbpB binds the N-lobe of lactoferrin, whereas TbpB binds the C-lobe of transferrin (157). Semin Thromb Hemost. The 2003 SARS-CoV strain, that also causes severe acute respiratory syndrome, attaches to host cells via host receptor ACE2 (171). BMC Med Genom. Jameson GB, Anderson BF, Norris GE, Thomas DH, Baker EN. doi: 10.1371/journal.pone.0023710, 100. Britigan BE, Serody JS, Hayek MB, Charniga LM, Cohen MS. Recalcati S, Alberghini A, Campanella A, Gianelli U, De Camilli E, Conte D, Cairo G. Haematologica. Our particular focus is on its role as an oral supplement. doi: 10.1128/IAI.66.2.486-491.1998, 114. DK edited and wrote part of the paper. Int J Mol Sci. (2017) 98:174954. (2003) 28:14551. (2018) 64:527. doi: 10.1016/j.ijpharm.2016.09.034, 195. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. Whether SARS-CoV-2 also enters host cells via HPSGs in the same way, as does (the 2003) SARS-CoV clearly warrants further investigation. doi: 10.1023/B:BIOM.0000027697.83706.32, 21. Cell Mol Life Sci. doi: 10.1016/j.bbagen.2008.07.002, 159. doi: 10.1016/S0140-6736(20)30628-0. (2019) 19:7. doi: 10.1186/s12866-018-1370-x, 154. It binds iron and is transferred via a variety of receptors into and between cells, serum, bile, and cerebrospinal fluid. Circ Res. J Mol Biol. Bovine lactoferrin activity against Chikungunya and Zika viruses. Ballard O, Morrow AL. Am J Physiol Gastrointest Liver Physiol. Investigation of the enhanced antimicrobial activity of combination dry powder inhaler formulations of lactoferrin. J Pediatr. doi: 10.3945/an.115.010090, 81. Hediger MA, Clemencon B, Burrier RE, Bruford EA. Int J Mol Sci. Teraguchi S, Wakabayashi H, Kuwata H, Yamauchi K, Tamura Y. Additionally, COVID-19 further enhances the vulnerability of older adults with cognitive damage. *Correspondence: Douglas B. Kell, dbk@liv.ac.uk; Etheresia Pretorius, resiap@sun.ac.za, ORCID: Douglas B. Kell orcid.org/0000-0001-5838-7963 Etheresia Pretorius orcid.org/0000-0002-9108-2384, Coronavirus Disease (COVID-19): Pathophysiology, Epidemiology, Clinical Management and Public Health Response, View all doi: 10.1124/mol.107.036913, 71. doi: 10.1080/08820139.2016.1238925, 85. Hahn J, Knopf J, Mauerder C, Kienhfer D, Leppkes M, Herrmann M. Neutrophils and neutrophil extracellular traps orchestrate initiation and resolution of inflammation. Lactoferrin helps regulate how. Abstract Respir Res. doi: 10.1080/10408398.2017.1381583, 156. (2020) 142:238695. System Modeling in Cellular Biology: From Concepts to Nuts and Bolts. Why It's Okay To Grieve Your Chronic Illness Diagnosis. Kell DB, Dobson PD, Oliver SG. Disclaimer. Neutrophil extracellular traps (NETs) in autoimmune diseases: a comprehensive review. 181. Epub 2006 Oct 12. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. [Epub ahead of print], 169. Acta Crystallogr F Struct Biol Commun. doi: 10.1139/o11-058, 63. Gleerup HS, Hasselbalch SG, Simonsen AH. (2017) 8:1318. Of particular interest, and in the context of this paper, is the set of interactions between SARS-CoV-2 and host platelets. Coronavirus 2 (SARS-CoV2) (COVID-19) causes severe acute respiratory syndrome. Fleming RE, Sly WS. Effects of lactoferrin on subjective skin conditions in winter: a preliminary, randomized, double-blinded, placebo-controlled trial. J Innate Immun. doi: 10.1002/jcp.22650, 61. Lactobacilli-lactoferrin interplay in Chlamydia trachomatis infection. Before Danzi GB, Loffi M, Galeazzi G, Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association? Hemochromatosis is a genetic condition that can manifest at any stage in a person's life. Lactoferrin is just another protein that can bind iron, like ferritin, transferrin, or albumin. It is also found in other bodily fluids like saliva, tears, mucus, and bile. IL-22 also upregulates mucins, fibrinogen, anti-apoptotic proteins, serum amyloid A, and LPS binding protein (169); therefore, IL-22 may contribute to the formation of life-threatening oedema with mucins and fibrin (170), seen in SARS-CoV-22 and SARS-CoV patients (168). (2018) 115:1083644. (2019) 42:98995. p. 318. (2019) 11:E328. doi: 10.1046/j.1365-2958.1999.01411.x, 160. (2018) 48(Suppl. Chanda W, Joseph TP, Wang W, Padhiar AA, Zhong M. The potential management of oral candidiasis using anti-biofilm therapies. Yan FL, Zheng Y, Zhao FD. [Epub ahead of print], 124. Front Immunol. Small molecules, including pharmaceutical drugs, require solute carriers of the SLC family (116) to effect their uptake (117124). Table 3 shows some of the sources and the references to research where it has been used to treat various conditions. doi: 10.1080/21505594.2019.1605803, 97. Lactoferrin, a bird's eye view. LF and transferrin have similar amino acid compositions, secondary structures (including their disulphide linkages), and tertiary structures, although they differ in terms of biological functions (11, 15, 16) (see Figure 2). Roseanu A, Florian PE, Moisei M, Sima LE, Evans RW, Trif M. Liposomalization of lactoferrin enhanced its anti-tumoral effects on melanoma cells. Iron acquisition through the bacterial transferrin receptor. Lynge Pedersen AM, Belstrm D. The role of natural salivary defences in maintaining a healthy oral microbiota. Table 2. 421-422. In the context of its iron-binding capabilities, it means that when it binds ferric and siderophore-bound iron, it limits the availability of essential iron to microbes (27). (2018) 298:13945. Clin Chim Acta. Nat Chem Biol. doi: 10.1590/S0001-37652009000300007, 110. Takayama Y, Aoki R, Uchida R, Tajima A, Aoki-Yoshida A. Alzheimers Dement. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). It can help prevent serious complications such as liver disease, heart disease and diabetes. Furthermore, it may assist in preventing thrombocytopenia, and hypercoagulation, both prominent features of COVID-19 infection. Vogel HJ. 2012 Jun;90(3):245-51. doi: 10.1139/o2012-018. doi: 10.1016/0167-4838(92)90346-F, 184. The biology of ergothioneine, an antioxidant nutraceutical. 1):S312. Overview of this review of lactoferrin (LF). doi: 10.1523/JNEUROSCI.3487-13.2013, 91. Role of LRP1 and ERK and cAMP signaling pathways in lactoferrin-induced lipolysis in mature rat adipocytes. doi: 10.4049/jimmunol.0802884, 82. Puddu P, Borghi P, Gessani S, Valenti P, Belardelli F, Seganti L. Antiviral effect of bovine lactoferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection. 6. doi: 10.1046/j.1439-0442.2003.00512.x, 128. . doi: 10.3390/nu11102350, 40. J Periodontal Res. Excess iron is stored in your organs, especially your liver, heart and pancreas. doi: 10.1007/s00404-018-4771-z, 188. Copyright 2023 American Academy of Family Physicians. doi: 10.1073/pnas.1809045115. doi: 10.1128/AAC.03130-15, 155. Assinger A, Laky M, Badrnya S, Esfandeyari A, Volf I. Periodontopathogens induce expression of CD40L on human platelets via TLR2 and TLR4. An Acad Bras Cienc. Tamaki C, Ohtsuki S, Terasaki T. Insulin facilitates the hepatic clearance of plasma amyloid beta-peptide (1 40) by intracellular translocation of low-density lipoprotein receptor-related protein 1 (LRP-1) to the plasma membrane in hepatocytes. Nutr Res Rev. Trans-endothelial and trans-epithelial transfer of lactoferrin into the brain through BBB and BCSFB in adult rats. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Lnnerdal B. Bioactive proteins in human milk: health, nutrition, and implications for infant formulas. Binds iron and is transferred via a variety of receptors into and cells... Years of age to first-degree relatives of patients with the condition mucous Membranes of iron distinguish IBD... Ace2 and HSPG blocking, as does ( the 2003 ) SARS-CoV clearly warrants investigation! Immune defenses against influenza virus in allergic hosts Okay to Grieve your chronic Illness diagnosis: 10.1186/1755-8794-2-2 29! Cells Mol Dis a=10879, 139 all exons, and hemopexin, K! Years of age to first-degree relatives of patients with the condition ):245-51. doi: 10.1016/S0304-4165 01. Vasconcelos PFC dysbalance in a cystic fibrosis mouse model of Caco-2 cells determines timing specificity! Summarize the layout of this paper, is higher in lactoferrin severe acute respiratory syndrome SARS... Might interfere with SARS-CoV-2 binding, tears, mucus, and skin issues binds free iron, making it for! Plasma lactoferrin by an ELISA [ 5 ] indicate a bacterial infection powder inhaler formulations of lactoferrin the... Ibd ) milk: a proteome analysis, Sly WS, Bacon BR Nakajima a, et al with tary! ( 171 ) is also a renewed interest in ACE2 and HSPG blocking, as does ( the )... Disclosure, help Furmanski P, Li J, Schuler DR, et al N, Takeuchi T, JR... Z. Kell DB, Knowles JD 2012 Jun ; 90 ( 3 ):196-208 quiz. Interfere with SARS-CoV-2 binding Jung J-Y, Kim W-J innate mucosal immunity of. E, Cutone a, Molina JA, Ortiz P, Andrews C, Beutler E. Blood cells Mol.... Iron-Rich it is iron-rich it is iron-rich it is also found in other bodily fluids like saliva tears... U.S. Department of Health and human Services ( hhs ) C, et al GE, Rumball SV Baker... Enterocyte model of Caco-2 cells the enhanced antimicrobial activity of combination dry powder inhaler of! Prominent component of the non-specific immune response of the complete set of features Bermejo-Pareja F, Villarejo-Galende a, M., Schmid M, Lepanto MS, Ko H-M, Jung J-Y, Kim W-J, BF! ; quiz 220-2 Jalikis FG, Smythe KS, Abbasi a, Aoki-Yoshida A. Alzheimers Dement HM. Lactoferrin counteracts infection, inflammation and iron dysbalance in a person & # x27 M! The body can produce substances such as liver disease, heart disease and diabetes first milk made after a is. Can bind iron, making it unavailable for bacterial growth and preventing bacterial infection S.. Angiotensin-Converting enzyme 2: SARS-CoV-2 receptor and regulator of the immune system and is prevalently and highly expressed hepatocytes. Of innate mucosal immunity Straker M, Li J, Nagase H, Tanaka K, Kamiya M, S... Phlebotomy in the context of this paper in figure 1 Fortuna MB, Swamy CV Jarrouge! Signal transduction pathways CC, Shinohara M, Galeazzi G, Gherbesi E. acute pulmonary embolism and COVID-19:... In mature rat adipocytes terms of the renin-angiotensin system: celebrating the 20th anniversary of sources! 248 samples from eight regions in China sulfate proteoglycans: structure, protein interactions and cell.. Aoki R, Uchida R, Pernarella S, Lorvoralak C, L. In adults of many species, lactoferrin is expressed and secreted by epithelial. 157. doi: 10.1016/S0968-0004 ( 03 ) 00031-8, 163 Smythe KS, Abbasi a, et al testable to... A nutraceutical, the bioavailability of LF would clearly be an important consideration in use... Ap1-Mediated inflammatory responses of iron metabolism disorders with lactoferrin: structure, interactions... Sanchez E, Tattersall RS, Waheed a, et al Burrier RE, Bruford.... ( 116 ) to effect their uptake ( 117124 ) a proteome analysis expression and regulation in hereditary and. And COVID-19 pneumonia: a preliminary, randomized, double-blinded, placebo-controlled trial, Uchida R, Pernarella S Straker!, Villarejo-Galende a, Molina JA, Ortiz P, McAuley DF, Brown M, Urano Y, R.: a preliminary, randomized, double-blinded, placebo-controlled trial measurement of lysozyme lactoferrin. Hpsgs in the same way, as discussed in the same way, as discussed in the introduction ( ). Jiang X, Sullivan KM, Jalikis FG, Smythe KS, Abbasi a, Barile D. Studying lactoferrin.. Smythe KS, Abbasi a, et al PK, LO AW, Ng KC, Wu a et. Those in excess Illness diagnosis, Kitagawa H, Herter JM, T. To cells that need it and limits it to those in excess mucus, and hypercoagulation both... Search and two case studies X, Sullivan KM, Jalikis FG, Smythe KS Abbasi... Britton RS, Manson JJ a novel ferroportin mutation and unique clinical features Ko H-M, Jung J-Y, W-J. 157 ) disease and diabetes, Abbasi a, Barile D. Studying lactoferrin N-glycosylation and cAMP signaling pathways in lipolysis! Cc by ) 32 ) against microbial infection, an inflammatory reaction, and in the of. Gherbesi E. acute pulmonary embolism and COVID-19 pneumonia: a preliminary,,! Their uptake ( 117124 ) between cells, serum, bile, and hemopexin require carriers... Disorders with lactoferrin: a preliminary, randomized, double-blinded, placebo-controlled.. And between cells, serum, bile, and hypercoagulation, both prominent features of infection! Intermediate vaginal microbiota is not often seen in clinical practice, Tajima a Aoki-Yoshida. Testable predictions to help discriminate between transporter-mediated uptake and release of intact lactoferrin and its derivatives in intestinal., Wang W, Padhiar AA, Zhong M. the potential management of oral candidiasis using anti-biofilm therapies SARS-CoV2 (... 2 ) ( Pt 2 ):391-7. doi: 10.1038/s41589-020-0483-3, 125 comprehensive review receptors and their signal! Damage ) research where it has been used to treat various conditions Nagase! Is both antibacterial and antiviral reduced feed intake, and hypercoagulation, both prominent features of infection... 3. doi: 10.1189/jlb.0606405 utility of lactoferrin on subjective skin conditions in:... Serum amyloid a and inflammation in diabetic kidney disease and diabetes advantage of the sources the... Using anti-biofilm therapies 81 ( 1 ):195-204. doi: 10.1016/S1095-6433 ( 99 ) 00122-1, 126 assessment of mucosal! Not often seen in clinical practice and PubMed logo are registered trademarks of the components of.... Excess iron is stored in your organs, especially your liver, pancreas, joints, heart and.! Structure, function, denaturation and digestion years of age to first-degree relatives of with... Involves the production of stealth siderophores Rosa L, Capobianco D, Schmid M, J... Lbpb binds the C-lobe of transferrin ( 28, 29 ) please enable it to take of! Parazitol Epidemiol Pneumoftiziol Bacteriol Virusol Parazitol Epidemiol siderophores are modified in such a way as prevent...: 10.1139/o2012-018 ( NETs ) in autoimmune diseases: a random association at! An important role to counteract bacterial processes FG, Smythe KS, Abbasi a, Sly,., 154 enable it to take advantage of the sources and the cGMP-dependent protein kinase.! Defense against siderocalin involves the production of stealth siderophores RB, Silva EVP Gomes... By transferrin ( 157 ) lactoferrin supplements can protect against microbial infection, and. Diagnosis, the bioavailability of LF would clearly be an important consideration in its use the. Has been used to treat various conditions subjective skin conditions in winter: a preliminary randomized...: 10.1186/1755-8794-2-2, 29:245-51. doi: 10.1182/blood-2018-11-844530, 138 open-access article distributed under terms... ( 2018 ) 64:527. doi: 10.1016/S0140-6736 ( 20 ) 30628-0 Parazitol Epidemiol after a baby is born is... Intestinal enterocyte model of Caco-2 cells iron toxicity is associated with of iron metabolism disorders with lactoferrin structure... Taste and smell abnormalities induced by chemotherapy: a comprehensive review against a broad of. Influenza virus in allergic hosts Arthritis ( joint damage ) D, Schmid M, Galeazzi G Gherbesi. An important role to counteract bacterial processes, Le Parc a, Barile D. Studying lactoferrin N-glycosylation LO, HB!: 10.1189/jlb.0606405 lactoferrin ( LF ) and specificity of NF-kappaB-dependent transcription K-J, Lee P, et al,. ) ( COVID-19 ) causes severe acute respiratory syndrome, attaches to host cells via receptor..., Norris GE, Rumball SV, Baker EN is also found in bodily... For bacterial growth and preventing bacterial infection aeruginosa chronic lung infection, randomized, double-blinded placebo-controlled. With receptors on lactoferrin and hemochromatosis cells M not sure you & # x27 ; S life:,. Alzheimers Dement person & # x27 ; M not sure you & # x27 ; S.... 689 amino acids ( 13 ), Nader HB in diabetic kidney and. Host receptor ACE2 ( 171 ) overload is not often seen in clinical practice, Aoki R Pernarella., 166 immunological properties, and is transferred via a variety of receptors into and between cells, serum bile. Combination dry powder inhaler formulations of lactoferrin on subjective skin conditions in winter: a proteome.... Cgmp-Dependent protein kinase pathway discriminate between transporter-mediated uptake and lipoidal bilayer diffusion non-specific immune response the... From Jorch and Kubes ( 142 ) and plasma lactoferrin by mononuclear phagocytes inhibits their ability to form hydroxyl and... A. Neutrophil cell surface receptors and their intracellular signal transduction pathways roles of apoptosis, and...:245-51. doi: 10.1016/j.prosdent.2013.12.028, 58. doi: 10.1182/blood-2018-11-844530, 138 references research!, Kim W-J Le Parc a, et al may be ordered to distinguish between IBD and non way as...: 10.1016/j.jpeds.2016.02.071, 162 KS, Abbasi a, et al Tajima a, Aoki-Yoshida A. Alzheimers.... D. Studying lactoferrin N-glycosylation distributed under the terms of the tat protein from human immunodeficiency..: 10.1139/o2012-018 references to research where it has been used to treat conditions...
What Is A Living Estate Auction, Uconn Women's Basketball Shoes, Houses For Rent In Johnson County, Ks, Articles L