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Fgl2  -  fibrinogen-like protein 2

Mus musculus

Synonyms: AI385601, Cytotoxic T-lymphocyte-specific protein, Fiblp, Fibrinogen-like protein 2, Fibroleukin, ...
 
 
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Disease relevance of Fgl2

 

High impact information on Fgl2

 

Chemical compound and disease context of Fgl2

  • While melanoma cells served as a suitable surface for prothrombinase complex formation, folate deficiency did not alter this membrane function, suggesting that the membrane changes associated with folate deficiency are relatively specific [8].
 

Biological context of Fgl2

  • Here, we demonstrate that Fgl2 expression is up-regulated during type 1 immunity in vivo and establish that such up-regulation is IFN gamma-, signal transducer and activation of transcription protein 1-, and IFN response factor 1-dependent [9].
  • Fgl2-deficient mice also reject allografts with similar kinetics as control mice [9].
  • CONCLUSIONS: Fgl2 appears to be physiologically expressed and may protect against the internal danger of maternal and/or fetal bleeding during pregnancy and at parturition; a role in inhibiting transplacental traffic is also possible [2].
  • In tissue from normal first trimester pregnancy, minimal Fgl2 positivity was seen in some villous syncytiotrophoblast, in villous stroma, cytotrophoblast, and in some cells in decidua [2].
  • By immunologic screening, a clone representing this prothrombinase was isolated from a cDNA library and sequenced [3].
 

Anatomical context of Fgl2

  • Prior studies found that Fgl2 is IFN gamma-inducible, possesses direct coagulant activity, and inhibits T cell proliferation and dendritic cell maturation in vitro [9].
  • Fgl2 prothrombinase expression in mouse trophoblast and decidua triggers abortion but may be countered by OX-2 [10].
  • RESULTS: Low level Fgl2 expression localized to basal decidua remote from the embryo was noted in control mice; cytokine treatment, which causes greater than 80% of abortions, produced a striking up-regulation in this area as well as in a band at the junction of decidua and myometrium [2].
  • PROBLEM: Abortion of chromosomally normal embryos in the CBA X DBA/2 mating combination is triggered by release of Th1 cytokines (tumor necrosis factor [TNF]-alpha, interferon [IFN]-gamma, and interleukin [IL]-1), which cause abortion via a novel prothrombinase, Fgl2, and polymorphonuclear leukocytes [2].
  • We asked where is Fgl2 up-regulated in the uterus in murine abortions, and if similar Fgl2 expression occurs in human pregnancy failure [2].
 

Associations of Fgl2 with chemical compounds

 

Physical interactions of Fgl2

 

Enzymatic interactions of Fgl2

 

Regulatory relationships of Fgl2

 

Other interactions of Fgl2

 

Analytical, diagnostic and therapeutic context of Fgl2

References

  1. The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis. Marsden, P.A., Ning, Q., Fung, L.S., Luo, X., Chen, Y., Mendicino, M., Ghanekar, A., Scott, J.A., Miller, T., Chan, C.W., Chan, M.W., He, W., Gorczynski, R.M., Grant, D.R., Clark, D.A., Phillips, M.J., Levy, G.A. J. Clin. Invest. (2003) [Pubmed]
  2. The emerging role of immunoregulation of fibrinogen-related procoagulant Fgl2 in the success or spontaneous abortion of early pregnancy in mice and humans. Clark, D.A., Ding, J.W., Chaouat, G., Coulam, C.B., August, C., Levy, G.A. Am. J. Reprod. Immunol. (1999) [Pubmed]
  3. Association of mouse fibrinogen-like protein with murine hepatitis virus-induced prothrombinase activity. Parr, R.L., Fung, L., Reneker, J., Myers-Mason, N., Leibowitz, J.L., Levy, G. J. Virol. (1995) [Pubmed]
  4. Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V. Cui, J., O'Shea, K.S., Purkayastha, A., Saunders, T.L., Ginsburg, D. Nature (1996) [Pubmed]
  5. Novel serine proteases encoded by two cytotoxic T lymphocyte-specific genes. Lobe, C.G., Finlay, B.B., Paranchych, W., Paetkau, V.H., Bleackley, R.C. Science (1986) [Pubmed]
  6. Expression and T cell recognition of hybrid antigens with amino-terminal domains encoded by Qa-2 region of major histocompatibility complex and carboxyl termini of transplantation antigens. Stroynowski, I., Forman, J., Goodenow, R.S., Schiffer, S.G., McMillan, M., Sharrow, S.O., Sachs, D.H., Hood, L. J. Exp. Med. (1985) [Pubmed]
  7. Murine lymphoid procoagulant activity induced by bacterial lipopolysaccharide and immune complexes is a monocyte prothrombinase. Schwartz, B.S., Levy, G.A., Fair, D.S., Edgington, T.S. J. Exp. Med. (1982) [Pubmed]
  8. Effects of nutritional folate deficiency on the adhesive properties of murine melanoma cells. Branda, R.F., Tracy, P.B. Cancer Lett. (1990) [Pubmed]
  9. Intact type 1 immunity and immune-associated coagulative responses in mice lacking IFN gamma-inducible fibrinogen-like protein 2. Hancock, W.W., Szaba, F.M., Berggren, K.N., Parent, M.A., Mullarky, I.K., Pearl, J., Cooper, A.M., Ely, K.H., Woodland, D.L., Kim, I.J., Blackman, M.A., Johnson, L.L., Smiley, S.T. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  10. Fgl2 prothrombinase expression in mouse trophoblast and decidua triggers abortion but may be countered by OX-2. Clark, D.A., Ding, J.W., Yu, G., Levy, G.A., Gorczynski, R.M. Mol. Hum. Reprod. (2001) [Pubmed]
  11. Kinetic analysis of a unique direct prothrombinase, fgl2, and identification of a serine residue critical for the prothrombinase activity. Chan, C.W., Chan, M.W., Liu, M., Fung, L., Cole, E.H., Leibowitz, J.L., Marsden, P.A., Clark, D.A., Levy, G.A. J. Immunol. (2002) [Pubmed]
  12. Ribavirin inhibits viral-induced macrophage production of TNF, IL-1, the procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response. Ning, Q., Brown, D., Parodo, J., Cattral, M., Gorczynski, R., Cole, E., Fung, L., Ding, J.W., Liu, M.F., Rotstein, O., Phillips, M.J., Levy, G. J. Immunol. (1998) [Pubmed]
  13. Loss of resistance to murine hepatitis virus strain 3 infection after treatment with corticosteroids is associated with induction of macrophage procoagulant activity. Fingerote, R.J., Abecassis, M., Phillips, M.J., Rao, Y.S., Cole, E.H., Leibowitz, J., Levy, G.A. J. Virol. (1996) [Pubmed]
  14. Induction of macrophage procoagulant activity by murine hepatitis virus strain 3: role of tyrosine phosphorylation. Dackiw, A.P., Zakrzewski, K., Nathens, A.B., Cheung, P.Y., Fingerote, R., Levy, G.A., Rotstein, O.D. J. Virol. (1995) [Pubmed]
  15. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Hamon, Y., Broccardo, C., Chambenoit, O., Luciani, M.F., Toti, F., Chaslin, S., Freyssinet, J.M., Devaux, P.F., McNeish, J., Marguet, D., Chimini, G. Nat. Cell Biol. (2000) [Pubmed]
  16. Basic residues of human group IIA phospholipase A2 are important for binding to factor Xa and prothrombinase inhibition comparison with other mammalian secreted phospholipases A2. Mounier, C.M., Luchetta, P., Lecut, C., Koduri, R.S., Faure, G., Lambeau, G., Valentin, E., Singer, A., Ghomashchi, F., Béguin, S., Gelb, M.H., Bon, C. Eur. J. Biochem. (2000) [Pubmed]
  17. Assembly and regulation of prothrombinase complex on B16F10 melanoma cells. Kirszberg, C., Rumjanek, V.M., Monteiro, R.Q. Thromb. Res. (2005) [Pubmed]
  18. Cellular and metabolic requirements for induction of macrophage procoagulant activity by murine hepatitis virus strain 3 in vitro. Chung, S., Sinclair, S., Leibowitz, J., Skamene, E., Fung, L.S., Levy, G. J. Immunol. (1991) [Pubmed]
  19. Why did your mother reject you? Immunogenetic determinants of the response to environmental selective pressure expressed at the uterine level. Clark, D.A., Arck, P.C., Chaouat, G. Am. J. Reprod. Immunol. (1999) [Pubmed]
  20. The cytotoxic T lymphocyte gene FIBLP with homology to fibrinogen beta and gamma subunits is also induced in mouse macrophages by IFN-gamma. Lafuse, W.P., Castle, L., Brown, D., Zwilling, B.S. Cell. Immunol. (1995) [Pubmed]
  21. Murine hepatitis virus strain 3 induces the macrophage prothrombinase fgl-2 through p38 mitogen-activated protein kinase activation. McGilvray, I.D., Lu, Z., Wei, A.C., Dackiw, A.P., Marshall, J.C., Kapus, A., Levy, G., Rotstein, O.D. J. Biol. Chem. (1998) [Pubmed]
  22. Factor VIIa-mediated tenase function on activated platelets under flow. Goel, M.S., Diamond, S.L. J. Thromb. Haemost. (2004) [Pubmed]
  23. The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction. Clark, D.A., Foerster, K., Fung, L., He, W., Lee, L., Mendicino, M., Markert, U.R., Gorczynski, R.M., Marsden, P.A., Levy, G.A. Mol. Hum. Reprod. (2004) [Pubmed]
  24. Novel mfgl2 antisense plasmid inhibits murine fgl2 expression and ameliorates murine hepatitis virus type 3-induced fulminant hepatitis in BALB/cJ mice. Zhu, C., Sun, Y., Luo, X., Yan, W., Xi, D., Ning, Q. Hum. Gene Ther. (2006) [Pubmed]
  25. Treatment of resistant A/J mice with methylprednisolone (MP) results in loss of resistance to murine hepatitis strain 3 (MHV-3) and induction of macrophage procoagulant activity (PCA). Fingerote, R.J., Leibowitz, J.L., Rao, Y.S., Levy, G.A. Adv. Exp. Med. Biol. (1995) [Pubmed]
 
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