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Gene Review

TF  -  transferrin

Bos taurus

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Disease relevance of TF

  • Pathogenic bacteria in the Neisseriaceae and Pasteurellaceae possess outer membrane proteins that specifically bind transferrin from the host as the first step in the iron acquisition process [1].
  • A weak reaction for transferrin (TF) was found in granulomas of a lymph node from one of the infected cattle [2].
  • Orally administered HSV-specific transfer factor (TF) prevents genital or labial herpes relapses [3].
  • Forty-four patients suffering from genital (22) and labial (22) herpes were orally treated with HSV-1/2-specific transfer factor (TF) [3].
  • Transfer factors (TF) were prepared from colostrum and milk of bovines previously immunized with antigens obtained from Coccidioides immitis, infectious bovine rhinotracheitis virus, or from the viral agents responsible for avian Newcastle disease, laryngotracheitis disease or infectious bursal disease [4].

Psychiatry related information on TF

  • Co-culture of Sc with peritubular myoid cells (Pc) significantly increased the secretion of both ABP and Trf, although the magnitude of stimulation and the time-response patterns were different for each protein [5].

High impact information on TF

  • The cell culture medium consisted of Medium 199 containing epidermal growth factor, triiodothyronine, hydrocortisone, Cohn fraction IV, insulin, transferrin, bovine brain extract, and trace elements [6].
  • This defined culture condition contains IL-7, the ligand for c-kit, transferrin, insulin, and bovine serum albumin as protein components [7].
  • This redistribution was accompanied by a faster rate of transferrin recycling from early endosomes to the cell surface and reduced transport to Rab11-containing perinuclear recycling endosomes [8].
  • Hub inhibition of clathrin-mediated membrane transport was established by demonstrating a block of transferrin internalization and an alteration in the intracellular distribution of the cation-independent mannose-6-phosphate receptor [9].
  • The sequence of ESAG7/6 differs slightly between different units, so that receptors with different affinities for Tf are expressed alternatively following transcriptional switching of VSG expression sites during antigenic variation of the parasite [10].

Chemical compound and disease context of TF


Biological context of TF

  • The ability of bovine TF to transfer specific cell-mediated immune responsiveness to a markedly xenogenic species was studied using specific pathogen free (SPF) and standard commercial (SC) chickens as model recipients [4].
  • As cellular immunity plays an important role in controlling herpes relapses, and other studies have shown the efficacy of HSV-specific transfer factor (TF) for the treatment of herpes patients, an open clinical trial was undertaken in 134 patients (71 keratitis, 29 kerato-uveitis, 34 uveitis) suffering from recurrent ocular herpetic infections [16].
  • When cells are plated in the total absence of serum, transferrin (10 micrograms/ml) is also required to induce optimal cell growth [17].
  • Endocytosis and intracellular transport has been studied in the bloodstream forms of Trypanosoma brucei by light and electron microscopy, using colloidal gold coupled to bovine transferrin (transferrin-gold) [18].
  • This observation indicates that EP cells do not need to reach confluence to undergo morphogenesis, and that HDL, which in the presence of transferrin supports the cell proliferation, can favor their differentiation into tubulelike structures once its concentration becomes limiting for mitogenesis [19].

Anatomical context of TF

  • In Experiment 1, ovarian cortical pieces from late-gestation bovine fetuses were cultured with 2, 5, 20, or 60% oxygen in Waymouth's medium plus ITS+ (insulin, transferrin, selenium plus linoleic acid and BSA) [20].
  • Presumptive zygotes were cultured in 1 of 3 culture media: 1) BSAITS - TCM 199 supplemented with 10 mg/ml BSA and ITS (5 mug/ml insulin, 5 mug/ml transferrin, and 5 ng/ml sodium selenite); 2) BECM - bovine embryo culture medium; and 3) BECM supplemented with ITS [21].
  • In contrast, bovine fibroblast growth factor caused a marked increase in the rate of TF plaque formation with IX-XI cells and only a slight increase with cells from III-V staged segments [22].
  • These findings raised the possibility that differences in the functional type of Sertoli cells from one location to another may account in part for the stage-related variation in TF release along the seminiferous tubule [22].
  • In additional experiments, we found that cultured cells from stage III-V and VII responded to FSH or isoproterenol with a large increase in the rate of TF plaque formation, whereas cells from IX-XI and XIII segments appeared to be unaffected [22].

Associations of TF with chemical compounds

  • When TF-GEN were exposed to increasing concentrations of (1-->3) beta-D glucan (beta-DG; 115 to 430 pg/ml) for 1 to 3 hours, concentration- and time-dependent increases in hydroxyl radical production were demonstrated by electron paramagnetic resonance spectrometry using 5, 5-dimethyl-1-pyrrolyne-N-oxide as a spin trap agent [23].
  • The present study evaluated the toxic effect of (1-->3) beta-D glucan, a major component of fungal cell wall, on cultured transformed glomerular endothelial cells (TF-GEN) [23].
  • When TF-GEN pretreated with U78517F (0.1 or 1.0 microM), a lipophilic antioxidant, were stimulated with LPS (1 or 10 microg/ml) or beta-DG (230 pg/ml) for 3 hours, free radical production by TF-GEN was significantly reduced in cells pretreated with the higher concentration of U78517F [23].
  • The combined results indicate that bovine TF specific for PPD is an oligoribonucleopeptide [24].
  • Use of transfer factor (TF) and nonspecific stimulators, such as Bacillus Calmette-Guerin ((BCG) vaccine, are examples [25].

Other interactions of TF


Analytical, diagnostic and therapeutic context of TF

  • Results obtained from immunocytochemical staining of cells from different sections agreed well with those obtained with plaque assays, indicating that we had detected most, if not all, TF cells in these cultures [22].
  • The total number of relapses was decreased significantly during/after TF treatment, dropping from 832 before, to 89 after treatment, whereas the cumulative relapse index (RI) dropped, during the same period, from 13.2 to 4.17 (P < 0.0001) [16].
  • Bovine TF activity eluted as a single peak after high-pressure reverse-phase liquid chromatography (HPLC); the active moiety contained at least one free co-planar cis-diol group, as shown by boronate affinity chromatography [24].
  • Blood samples for full blood count, serum ferritin (SF), serum iron (SI) and transferrin (TF) level estimations were obtained by venesection [31].
  • Uptake and transfer of maternal transferrin by rat embryos during organogenesis in vitro was investigated using radiolabelled rat transferrin and rocket immunoelectrophoresis [32].


  1. Production and characterization of chimeric transferrins for the determination of the binding domains for bacterial transferrin receptors. Retzer, M.D., Kabani, A., Button, L.L., Yu, R.H., Schryvers, A.B. J. Biol. Chem. (1996) [Pubmed]
  2. The distribution of ferritin, lactoferrin and transferrin in granulomatous lymphadenitis of bovine paratuberculosis. Momotani, E., Whipple, D.L., Thiermann, A.B. J. Comp. Pathol. (1988) [Pubmed]
  3. Orally administered HSV-specific transfer factor (TF) prevents genital or labial herpes relapses. Pizza, G., Viza, D., De Vinci, C., Palareti, A., Cuzzocrea, D., Fornarola, V., Baricordi, R. Biotherapy (Dordrecht, Netherlands) (1996) [Pubmed]
  4. De novo initiation of specific cell-mediated immune responsiveness in chickens by transfer factor (specific immunity inducer) obtained from bovine colostrum and milk. Wilson, G.B., Poindexter, C., Fort, J.D., Ludden, K.D. Acta Virol. (1988) [Pubmed]
  5. Vectorial secretion of transferrin and androgen binding protein in Sertoli cell cultures: effect of extracellular matrix, peritubular myoid cells and medium composition. Janecki, A., Steinberger, A. Mol. Cell. Endocrinol. (1987) [Pubmed]
  6. An endocrine approach to the control of epidermal growth: serum-free cultivation of human keratinocytes. Maciag, T., Nemore, R.E., Weinstein, R., Gilchrest, B.A. Science (1981) [Pubmed]
  7. Cell cycle control of c-kit+IL-7R+ B precursor cells by two distinct signals derived from IL-7 receptor and c-kit in a fully defined medium. Yasunaga, M., Wang, F., Kunisada, T., Nishikawa, S., Nishikawa, S. J. Exp. Med. (1995) [Pubmed]
  8. Divalent Rab effectors regulate the sub-compartmental organization and sorting of early endosomes. de Renzis, S., Sönnichsen, B., Zerial, M. Nat. Cell Biol. (2002) [Pubmed]
  9. A dominant-negative clathrin mutant differentially affects trafficking of molecules with distinct sorting motifs in the class II major histocompatibility complex (MHC) pathway. Liu, S.H., Marks, M.S., Brodsky, F.M. J. Cell Biol. (1998) [Pubmed]
  10. Characterization of the ligand-binding site of the transferrin receptor in Trypanosoma brucei demonstrates a structural relationship with the N-terminal domain of the variant surface glycoprotein. Salmon, D., Hanocq-Quertier, J., Paturiaux-Hanocq, F., Pays, A., Tebabi, P., Nolan, D.P., Michel, A., Pays, E. EMBO J. (1997) [Pubmed]
  11. Mechanisms of estrogen action on the proliferation of MCF-7 human breast cancer cells in an improved culture medium. Furuya, Y., Kohno, N., Fujiwara, Y., Saitoh, Y. Cancer Res. (1989) [Pubmed]
  12. Characterization of the mucin differentiation in human lung adenocarcinoma cell lines. Yang, P.C., Luh, K.T., Wu, R., Wu, C.W. Am. J. Respir. Cell Mol. Biol. (1992) [Pubmed]
  13. Effect of melanocyte stimulating hormone on human cultured choroidal melanocytes, uveal melanoma cells, and retinal epithelial cells. Goodall, T., Buffey, J.A., Rennie, I.G., Benson, M., Parsons, M.A., Faulkner, M.K., MacNeil, S. Invest. Ophthalmol. Vis. Sci. (1994) [Pubmed]
  14. Development of a serum-free medium which supports the long-term growth of human and nonhuman primate lymphoid cells. Brown, R.L., Griffith, R.L., Neubauer, R.H., Rabin, H. J. Cell. Physiol. (1983) [Pubmed]
  15. Effect of serum albumin on siderophore-mediated utilization of transferrin iron. Konopka, K., Neilands, J.B. Biochemistry (1984) [Pubmed]
  16. Efficacy of transfer factor in treating patients with recurrent ocular herpes infections. Meduri, R., Campos, E., Scorolli, L., De Vinci, C., Pizza, G., Viza, D. Biotherapy (Dordrecht, Netherlands) (1996) [Pubmed]
  17. Factors controlling the proliferative rate, final cell density, and life span of bovine vascular smooth muscle cells in culture. Gospodarowicz, D., Hirabayashi, K., Giguère, L., Tauber, J.P. J. Cell Biol. (1981) [Pubmed]
  18. Intracellular colocalization of variant surface glycoprotein and transferrin-gold in Trypanosoma brucei. Webster, P., Grab, D.J. J. Cell Biol. (1988) [Pubmed]
  19. Comparison of the ability of basement membranes produced by corneal endothelial and mouse-derived Endodermal PF-HR-9 cells to support the proliferation and differentiation of bovine kidney tubule epithelial cells in vitro. Gospodarowicz, D., Lepine, J., Massoglia, S., Wood, I. J. Cell Biol. (1984) [Pubmed]
  20. Effects of oxygen tension and supplements to the culture medium on activation and development of bovine follicles in vitro. Gigli, I., Byrd, D.D., Fortune, J.E. Theriogenology (2006) [Pubmed]
  21. Effects of sperm treatments on the in vitro development of bovine oocytes in semidefined and defined media. Jaakma, U., Zhang, B.R., Larsson, B., Niwa, K., Rodriguez-Martinez, H. Theriogenology (1997) [Pubmed]
  22. Sertoli cell function varies along the seminiferous tubule: the proportion and response of transferrin secretors differ between stage-associated tubule segments. Garza, M.M., Schwarz, L.K., Bonner, J.M., Boockfor, F.R. Endocrinology (1991) [Pubmed]
  23. Glomerular endothelial injury associated with free radical production induced by a fungal cell wall component, (1-->3) beta-D glucan. Iwamoto, N., Yoshioka, T., Nitta, K., Ito, K. Life Sci. (1998) [Pubmed]
  24. Bovine 'transfer factor': an oligoribonucleopeptide which initiates antigen-specific lymphocytes responsiveness. Wilson, G.B., Paddock, G.V., Fudenberg, H.H. Thymus (1982) [Pubmed]
  25. Developments in immunotherapy. Krakowka, S. Modern veterinary practice. (1981) [Pubmed]
  26. Polymorphisms in blood proteins of Bos indicus and Bos taurus cattle breeds of Cameroon and Nigeria, and description of new albumin variants. Ibeagha-Awemu, E.M., Jäger, S., Erhardt, G. Biochem. Genet. (2004) [Pubmed]
  27. Regulation of Fas antigen (Fas, CD95)-mediated apoptosis of bovine granulosa cells by serum and growth factors. Quirk, S.M., Harman, R.M., Cowan, R.G. Biol. Reprod. (2000) [Pubmed]
  28. Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges. Isshiki, M., Ando, J., Korenaga, R., Kogo, H., Fujimoto, T., Fujita, T., Kamiya, A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  29. Continuous culture and soft agarose cloning of multiple human breast carcinoma cell lines in serum-free medium. Calvo, F., Brower, M., Carney, D.N. Cancer Res. (1984) [Pubmed]
  30. Constitutive lysosomal targeting and degradation of bovine endothelin-converting enzyme-1a mediated by novel signals in its alternatively spliced cytoplasmic tail. Emoto, N., Nurhantari, Y., Alimsardjono, H., Xie, J., Yamada, T., Yanagisawa, M., Matsuo, M. J. Biol. Chem. (1999) [Pubmed]
  31. Iron status and dietary iron intake of 6-24-month-old children in Adelaide. Oti-Boateng, P., Seshadri, R., Petrick, S., Gibson, R.A., Simmer, K. Journal of paediatrics and child health. (1998) [Pubmed]
  32. Maternal transferrin uptake by and transfer across the visceral yolk sac of the early postimplantation rat conceptus in vitro. Huxham, I.M., Beck, F. Dev. Biol. (1985) [Pubmed]
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