Bravo Probiotics 

What Is A Macrophage?

Macrophages are so named from the Greek term ‘big eaters’.  They are effectively the ‘big guns’ in the immune system and are called into play by the T and B cells, releasing their enzymes, which in turn create GcMAF.  This is the signal, or key, for the macrophages to wake up and join in the fight.  Just as in human warfare, the big equipment is not deployed for every skirmish, and so the same thing applies, in principle, in the immune system.  In the absence of GcMAF, macrophages bimble around, eating enough to stay alive.  Once activated with MAF (macrophage activating factor), macrophages increase their consumption rate over 15 times.  In addition, whilst consuming pathogens, they also send off chemical signals to other immune cells to bring them into play.  In this way, macrophages are very, very important in the immune system.

Some cancers and viruses stimulate production of an enzyme known as nagalase, which will prevent the body from producing GcMAF.  It does this by destroying the site on the Gc protein that would have generated the GcMAF.  While nagalase circulates in the body, it causes a suppression of the immune system by preventing the activation of macrophages .  This is known as immunosuppression.  By increasing the effectiveness of the immune system, this in turn can reduce the viruses and cancers, which then reduces the amount of circulating nagalase.

How GcMAF Works In Our Cells?

In this amazing video you can see the actual proof with your own eye how the GcMAF activated Macrophages distroy the cancer cells! Must watch!!!

Three More Research Papers

(click on the images below to see) 

Science

As of February 2013, on the American National Library of Medicine alone, 142 eminent scientists from 8 nations have published 59 major GcMAF research papers. These can be viewed on the US Government’s Pubmed system

Here is the list on the US Library of Medicine, http://www.ncbi.nlm.nih.gov/pubmed searching on:
GcMAF OR “vitamin D binding protein” AND “macrophage activating factor

1: Toyohara Y, Hashitani S, Kishimoto H, Noguchi K, Yamamoto N, Urade M. Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line. Oncol Lett. 2011 Jul;2(4):685-691. Epub 2011 May 13. PubMed PMID: 22848250; PubMed Central PMCID: PMC3406437.

2: Bellone M, Rigamonti N. Vitamin D-binding protein-derived macrophage-activating factor, GcMAF, and prostate cancer. Cancer Immunol Immunother. 2012 Dec;61(12):2377-8. doi: 10.1007/s00262-012-1310-9. Epub 2012 Jun 28. PubMed PMID: 22740161.

3: Uto Y, Yamamoto S, Mukai H, Ishiyama N, Takeuchi R, Nakagawa Y, Hirota K, Terada H, Onizuka S, Hori H. ?-Galactosidase treatment is a common first-stage modification of the three major subtypes of Gc protein to GcMAF. Anticancer Res. 2012 Jun;32(6):2359-64. PubMed PMID: 22641675.

4: Pacini S, Punzi T, Morucci G, Gulisano M, Ruggiero M. Effects of vitamin D-binding protein-derived macrophage-activating factor on human breast cancer cells. Anticancer Res. 2012 Jan;32(1):45-52. PubMed PMID: 22213287.

5: Pacini S, Morucci G, Punzi T, Gulisano M, Ruggiero M, Amato M, Aterini S. Effect of paricalcitol and GcMAF on angiogenesis and human peripheral blood mononuclear cell proliferation and signaling. J Nephrol. 2012 Jul-Aug;25(4):577-81. doi: 10.5301/jn.5000035. PubMed PMID: 21956771.

6: Uto Y, Yamamoto S, Takeuchi R, Nakagawa Y, Hirota K, Terada H, Onizuka S, Nakata E, Hori H. Effect of the Gc-derived macrophage-activating factor precursor (preGcMAF) on phagocytic activation of mouse peritoneal macrophages. Anticancer
Res. 2011 Jul;31(7):2489-92. PubMed PMID: 21873164.

7: Debruyne E, Speeckaert M, Weygaerde YV, Delanghe J. Phenotype of Gc-globulin influences the macrophage activating factor (MAF) levels in serum. Clin Chem Lab Med. 2011 Nov;49(11):1855-60. doi: 10.1515/CCLM.2011.676. Epub 2011 Aug 23. PubMed PMID: 21859424.

8: Pacini S, Morucci G, Punzi T, Gulisano M, Ruggiero M. Gc protein-derived macrophage-activating factor (GcMAF) stimulates cAMP formation in human mononuclear cells and inhibits angiogenesis in chick embryo chorionallantoic
membrane assay. Cancer Immunol Immunother. 2011 Apr;60(4):479-85. doi: 10.1007/s00262-010-0953-7. Epub 2010 Dec 14. PubMed PMID: 21170647.

9: Faserl K, Golderer G, Kremser L, Lindner H, Sarg B, Wildt L, Seeber B. Polymorphism in vitamin D-binding protein as a genetic risk factor in the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2011 Jan;96(1):E233-41. doi: 10.1210/jc.2010-1532. Epub 2010 Oct 27. PubMed PMID: 20980430.

10: Gregory KJ, Zhao B, Bielenberg DR, Dridi S, Wu J, Jiang W, Huang B, Pirie-Shepherd S, Fannon M. Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells. PLoS One. 2010 Oct 18;5(10):e13428. doi: 10.1371/journal.pone.0013428. PubMed PMID: 20976141; PubMed Central PMCID: PMC2956649.

11: Nonaka K, Onizuka S, Ishibashi H, Uto Y, Hori H, Nakayama T, Matsuura N, Kanematsu T, Fujioka H. Vitamin D binding protein-macrophage activating factor inhibits HCC in SCID mice. J Surg Res. 2012 Jan;172(1):116-22. doi: 10.1016/j.jss.2010.07.057. Epub 2010 Sep 17. PubMed PMID: 20855083.

12: Ravnsborg T, Olsen DT, Thysen AH, Christiansen M, Houen G, Højrup P. The glycosylation and characterization of the candidate Gc macrophage activating factor. Biochim Biophys Acta. 2010 Apr;1804(4):909-17. doi: 10.1016/j.bbapap.2009.12.022. Epub 2010 Jan 13. PubMed PMID: 20079467.

13: Rehder DS, Nelson RW, Borges CR. Glycosylation status of vitamin D binding protein in cancer patients. Protein Sci. 2009 Oct;18(10):2036-42. doi: 10.1002/pro.214. PubMed PMID: 19642159; PubMed Central PMCID: PMC2786967.

14: Fang Y, van Meurs JB, Arp P, van Leeuwen JP, Hofman A, Pols HA, Uitterlinden AG. Vitamin D binding protein genotype and osteoporosis. Calcif Tissue Int. 2009 Aug;85(2):85-93. doi: 10.1007/s00223-009-9251-9. Epub 2009 Jun 2. PubMed PMID: 19488670; PubMed Central PMCID: PMC2729412.

15: Yamamoto N, Ushijima N, Koga Y. Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF). J Med Virol. 2009 Jan;81(1):16-26. doi: 10.1002/jmv.21376. PubMed PMID: 19031451.

16: Yamamoto N, Suyama H, Yamamoto N. Immunotherapy for Prostate Cancer with Gc Protein-Derived Macrophage-Activating Factor, GcMAF. Transl Oncol. 2008 Jul;1(2):65-72. PubMed PMID: 18633461; PubMed Central PMCID: PMC2510818.

17: Spiriti J, Bogani F, van der Vaart A, Ghirlanda G. Modulation of protein stability by O-glycosylation in a designed Gc-MAF analog. Biophys Chem. 2008 May;134(3):157-67. doi: 10.1016/j.bpc.2008.02.005. Epub 2008 Feb 21. PubMed PMID:
18329161.

18: Yamamoto N, Suyama H, Nakazato H, Yamamoto N, Koga Y. Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF. Cancer Immunol Immunother. 2008
Jul;57(7):1007-16. PubMed PMID: 18058096.

19: Yamamoto N, Suyama H, Yamamoto N, Ushijima N. Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF). Int J Cancer. 2008 Jan 15;122(2):461-7. PubMed PMID:
17935130.

20: Meier U, Gressner O, Lammert F, Gressner AM. Gc-globulin: roles in response to injury. Clin Chem. 2006 Jul;52(7):1247-53. Epub 2006 May 18. Review. PubMed PMID: 16709624.

21: Kalkunte S, Brard L, Granai CO, Swamy N. Inhibition of angiogenesis by vitamin D-binding protein: characterization of anti-endothelial activity of DBP-maf. Angiogenesis. 2005;8(4):349-60. Epub 2006 Jan 7. PubMed PMID: 16400520.

22: Yamamoto N, Urade M. Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the hemagglutinin of influenza virus. Microbes Infect. 2005 Apr;7(4):674-81. Epub 2005 Mar 22. PubMed PMID: 15848273.

23: Nagasawa H, Sasaki H, Uto Y, Kubo S, Hori H. Association of the macrophage activating factor (MAF) precursor activity with polymorphism in vitamin D-binding protein. Anticancer Res. 2004 Sep-Oct;24(5C):3361-6. PubMed PMID: 15515432.

24: Onizuka S, Kawakami S, Taniguchi K, Fujioka H, Miyashita K. Pancreatic carcinogenesis: apoptosis and angiogenesis. Pancreas. 2004 Apr;28(3):317-9. PubMed PMID: 15084979.

25: Matsuura T, Uematsu T, Yamaoka M, Furusawa K. Effect of salivary gland adenocarcinoma cell-derived alpha-N-acetylgalactosaminidase on the bioactivity of macrophage activating factor. Int J Oncol. 2004 Mar;24(3):521-8. PubMed PMID: 14767536.

26: Schneider GB, Grecco KJ, Safadi FF, Popoff SN. The anabolic effects of vitamin D-binding protein-macrophage activating factor (DBP-MAF) and a novel small peptide on bone. Crit Rev Eukaryot Gene Expr. 2003;13(2-4):277-84. PubMed
PMID: 14696974.

27: Mohamad SB, Nagasawa H, Sasaki H, Uto Y, Nakagawa Y, Kawashima K, Hori H. Gc protein-derived macrophage activating factor (GcMAF): isoelectric focusing pattern and tumoricidal activity. Anticancer Res. 2003 Nov-Dec;23(6a):4451-7. PubMed PMID: 14666733.

28: Gumireddy K, Reddy CD, Swamy N. Mitogen-activated protein kinase pathway mediates DBP-maf-induced apoptosis in RAW 264.7 macrophages. J Cell Biochem. 2003 Sep 1;90(1):87-96. PubMed PMID: 12938159.

29: Kisker O, Onizuka S, Becker CM, Fannon M, Flynn E, D’Amato R, Zetter B, Folkman J, Ray R, Swamy N, Pirie-Shepherd S. Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice.
Neoplasia. 2003 Jan-Feb;5(1):32-40. PubMed PMID: 12659668; PubMed Central PMCID: PMC1502120.

30: Mohamad SB, Nagasawa H, Uto Y, Hori H. Preparation of Gc protein-derived macrophage activating factor (GcMAF) and its structural characterization and biological activities. Anticancer Res. 2002 Nov-Dec;22(6C):4297-300. PubMed PMID:
12553073.

31: Kanda S, Mochizuki Y, Miyata Y, Kanetake H, Yamamoto N. Effects of vitamin D(3)-binding protein-derived macrophage activating factor (GcMAF) on angiogenesis. J Natl Cancer Inst. 2002 Sep 4;94(17):1311-9. PubMed PMID: 12208896.

32: Swamy N, Ghosh S, Schneider GB, Ray R. Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity. J Cell Biochem. 2001;81(3):535-46. PubMed PMID: 11255236.

33: Kanan RM, Cook DB, Datta HK. Lectin immunoassay for macrophage-activating factor (Gc-MAF) produced by deglycosylation of Gc-globulin: evidence for noninducible generation of Gc-MAF. Clin Chem. 2000 Mar;46(3):412-4. PubMed PMID: 10702530.

34: Odgren PR, Popoff SN, Safadi FF, MacKay CA, Mason-Savas A, Seifert MF, Marks SC Jr. The toothless osteopetrotic rat has a normal vitamin D-binding protein-macrophage activating factor (DBP-MAF) cascade and chondrodysplasia resistant to treatments with colony stimulating factor-1 (CSF-1) and/or DBP-MAF. Bone. 1999 Aug;25(2):175-81. PubMed PMID: 10456382.

35: Koga Y, Naraparaju VR, Yamamoto N. Antitumor effect of vitamin D-binding protein-derived macrophage activating factor on Ehrlich ascites tumor-bearing mice. Proc Soc Exp Biol Med. 1999 Jan;220(1):20-6. PubMed PMID: 9893164.

36: Adebanjo OA, Moonga BS, Haddad JG, Huang CL, Zaidi M. A possible new role for vitamin D-binding protein in osteoclast control: inhibition of extracellular Ca2+ sensing at low physiological concentrations. Biochem Biophys Res Commun. 1998 Aug 28;249(3):668-71. PubMed PMID: 9731194.

37: Yamamoto N, Naraparaju VR. Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization. Immunol Cell Biol. 1998 Jun;76(3):237-44. PubMed PMID: 9682967.

38: Yamamoto N, Naraparaju VR. Immunotherapy of BALB/c mice bearing Ehrlich ascites tumor with vitamin D-binding protein-derived macrophage activating factor. Cancer Res. 1997 Jun 1;57(11):2187-92. PubMed PMID: 9187119.

39: Yamamoto N, Naraparaju VR, Moore M, Brent LH. Deglycosylation of serum vitamin D3-binding protein by alpha-N-acetylgalactosaminidase detected in the plasma of patients with systemic lupus erythematosus. Clin Immunol Immunopathol.
1997 Mar;82(3):290-8. PubMed PMID: 9073553.

40: Yamamoto N, Naraparaju VR, Urade M. Prognostic utility of serum alpha-N-acetylgalactosaminidase and immunosuppression resulted from deglycosylation of serum Gc protein in oral cancer patients. Cancer Res. 1997 Jan
15;57(2):295-9. PubMed PMID: 9000571.

41: Korbelik M, Naraparaju VR, Yamamoto N. Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer. Br J Cancer. 1997;75(2):202-7. PubMed PMID: 9010027; PubMed Central PMCID: PMC2063270.

42: Benis KA, Schneider GB. The effects of vitamin D binding protein-macrophage activating factor and colony-stimulating factor-1 on hematopoietic cells in normal and osteopetrotic rats. Blood. 1996 Oct 15;88(8):2898-905. PubMed PMID:
8874186.

43: Yamamoto N. Structural definition of a potent macrophage activating factor derived from vitamin D3-binding protein with adjuvant activity for antibody production. Mol Immunol. 1996 Oct;33(15):1157-64. PubMed PMID: 9070663.

44: Yamamoto N, Naraparaju VR. Role of vitamin D3-binding protein in activation of mouse macrophages. J Immunol. 1996 Aug 15;157(4):1744-9. PubMed PMID: 8759764.

45: Yamamoto N, Naraparaju VR, Orchard PJ. Defective lymphocyte glycosidases in the macrophage activation cascade of juvenile osteopetrosis. Blood. 1996 Aug 15;88(4):1473-8. PubMed PMID: 8695868.

46: Yamamoto N, Naraparaju VR. A defect in inducible beta-galactosidase of B lymphocytes in the osteopetrotic (mi/mi) mouse. Immunology. 1996 Aug;88(4):604-10. PubMed PMID: 8881764; PubMed Central PMCID: PMC1456628.

47: Yamamoto N, Naraparaju VR, Asbell SO. Deglycosylation of serum vitamin D3-binding protein leads to immunosuppression in cancer patients. Cancer Res. 1996 Jun 15;56(12):2827-31. PubMed PMID: 8665521.

48: Yamamoto N, Naraparaju VR. Vitamin D3-binding protein as a precursor for macrophage activating factor in the inflammation-primed macrophage activation cascade in rats. Cell Immunol. 1996 Jun 15;170(2):161-7. PubMed PMID: 8660814.

49: Yamamoto N, Naraparaju VR. A defect in beta-galactosidase of B lymphocytes in the osteopetrotic (op/op) mouse. Immunol Lett. 1996 Apr;50(1-2):35-40. PubMed PMID: 8793557.

50: Yamamoto N, Naraparaju VR, Srinivasula SM. Structural modification of serum vitamin D3-binding protein and immunosuppression in AIDS patients. AIDS Res Hum Retroviruses. 1995 Nov;11(11):1373-8. PubMed PMID: 8573395.

51: Schneider GB, Benis KA, Flay NW, Ireland RA, Popoff SN. Effects of vitamin D binding protein-macrophage activating factor (DBP-MAF) infusion on bone resorption in two osteopetrotic mutations. Bone. 1995 Jun;16(6):657-62. PubMed
PMID: 7669443.

52: Naraparaju VR, Yamamoto N. Roles of beta-galactosidase of B lymphocytes and sialidase of T lymphocytes in inflammation-primed activation of macrophages. Immunol Lett. 1994 Dec;43(3):143-8. PubMed PMID: 7721326.

53: Yamamoto N, Willett NP, Lindsay DD. Participation of serum proteins in the inflammation-primed activation of macrophages. Inflammation. 1994 Jun;18(3):311-22. PubMed PMID: 8088927.

54: Yamamoto N, Lindsay DD, Naraparaju VR, Ireland RA, Popoff SN. A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats. J Immunol. 1994 May 15;152(10):5100-7. PubMed PMID: 8176226.

55: Yamamoto N, Kumashiro R. Conversion of vitamin D3 binding protein (group-specific component) to a macrophage activating factor by the stepwise action of beta-galactosidase of B cells and sialidase of T cells. J Immunol. 1993 Sep 1;151(5):2794-802. PubMed PMID: 8360493.

56: Homma S, Yamamoto M, Yamamoto N. Vitamin D-binding protein (group-specific component) is the sole serum protein required for macrophage activation after treatment of peritoneal cells with lysophosphatidylcholine. Immunol Cell Biol. 1993 Aug;71 ( Pt 4):249-57. PubMed PMID: 8225394.

57: Yamamoto N, Homma S, Haddad JG, Kowalski MA. Vitamin D3 binding protein required for in vitro activation of macrophages after alkylglycerol treatment of mouse peritoneal cells. Immunology. 1991 Nov;74(3):420-4. PubMed PMID: 1769691; PubMed Central PMCID: PMC1384634.

58: Yamamoto N, Homma S. Vitamin D3 binding protein (group-specific component) is a precursor for the macrophage-activating signal factor from lysophosphatidylcholine-treated lymphocytes. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8539-43. PubMed PMID: 1924312; PubMed Central PMCID: PMC52544.

59: Yamamoto N, Homma S, Millman I. Identification of the serum factor required for in vitro activation of macrophages. Role of vitamin D3-binding protein (group specific component, Gc) in lysophospholipid activation of mouse peritoneal
macrophages. J Immunol. 1991 Jul 1;147(1):273-80. PubMed PMID: 2051023.


"Researchers and practitioners have demonstrated that GcMAF can reverse diseases that attack the immune system such as: chronic inflammation, bacterial and viral infections, chronic herpes, chronic acne, Lyme disease, fibromyalgia osteoporosis, Hodgkin's, Lupus, MS, Parkinson's and remarkably – autism."

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