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Expression of Fc Fragment Receptors of Immunoglobulin G (FcγRs) in Rat Hepatic Stellate Cells

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Hepatic stellate cells (HSCs) are now considered the major cell type in the liver mediating the development of liver fibrosis. Recently it was demonstrated that HSCs express membrane proteins involved in antigen presentation. We further evaluate immunological properties of HSCs by examining the expression and function of the Fc fragment of immunoglobulin G (IgG) in HSCs. In this study, we document the presence of mRNAs for three FcγRs in HSCs. Ligand binding assay indicated the existence of FcγRs with different binding affinities on membranes of HSCs. We also documented that the abundance of the three Fcγ R mRNAs increased upon activation of HSCs in vitro. Moreover, an examination of the biological activities of IgG revealed that exposure to IgG significantly stimulated HSC differentiation and proliferation. Furthermore, we studied the intracellular signaling protein, LcK, in HSCs and regulation of Lck expression and phosphorylation by IgG. Although IgG did not regulate Lck abundance and phosphorylation in HSCs, highly phosphorylated Lck was present in these cells. In conclusion, we provided evidence that HSCs expresses receptors for the Fc fragment of IgG, and IgG regulates HSC differentiation and proliferation. Therefore, immunoglobulin G may play a role in HSC activation.

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References

  1. Friedman SL: Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 275(4):2247–2250, 2000

    Article  PubMed  CAS  Google Scholar 

  2. Gressner AM: The up-and-down of hepatic stellate cells in tissue injury: apoptosis restores cellular homeostasis. Gastroenterology 120(5):1285–1288, 2001

    PubMed  CAS  Google Scholar 

  3. Reeves HL, Friedman SL: Activation of hepatic stellate cells—A key issue in liver fibrosis. Front Biosci 7:d808–d826, 2002

    Article  PubMed  CAS  Google Scholar 

  4. Pinzani M: Liver fibrosis. Springer Semin Immunopathol 21(4):475–490, 1999

    Article  PubMed  CAS  Google Scholar 

  5. Rockey DC: Hepatic blood flow regulation by stellate cells in normal and injured liver. Semin Liver Dis 21(3):337–349, 2001

    Article  PubMed  CAS  Google Scholar 

  6. Reynaert H, Thompson MG, Thomas T, Geerts A: Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension. Gut 50(4):571–581, 2002

    Article  PubMed  CAS  Google Scholar 

  7. Vinas O, Bataller R, Sancho-Bru P, et al. : Human hepatic stellate cells show features of antigen-presenting cells and stimulate lymphocyte proliferation. Hepatology 38(4):919–929, 2003

    PubMed  CAS  Google Scholar 

  8. Torok NJ, Taimr P, Friedman SL, Gore GJ: Hepatocyte apoptosis enhances fibrogenic activity of human stellate cells following engulfment of apoptotic bodies. A novel link between two key features of chronic liver disease. Hepatology 34:153A, 2001 (abstr)

    Google Scholar 

  9. Gessner JE, Heiken H, Tamm A, Schmidt RE: The IgG Fc receptor family. Ann Hematol 76(6):231–248, 1998

    Article  PubMed  CAS  Google Scholar 

  10. Greenberg S: Modular components of phagocytosis. J Leukoc Biol 66(5):712–717, 1999

    PubMed  CAS  Google Scholar 

  11. Morel PA, Ernst LK, Metes D: Functional CD32 molecules on human NK cells. Leuk Lymphoma 35(1–2):47–56, 1999

    Article  PubMed  CAS  Google Scholar 

  12. Tuijnman WB, Van Wichen DF, Schuurman HJ: Tissue distribution of human IgG Fc receptors CD16, CD32 and CD64: an immunohistochemical study. Apmis 101(4):319–329, 1993

    Article  PubMed  CAS  Google Scholar 

  13. Shen H, Huang G, Hadi M, et al. : Transforming growth factor-beta1 downregulation of Smad1 gene expression in rat hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 285(3):G539–G546, 2003

    PubMed  CAS  Google Scholar 

  14. Gavin AL, Hamilton JA, Hogarth PM: Extracellular mutations of non-obese diabetic mouse FcgammaRI modify surface expression and ligand binding. J Biol Chem 271(29):17091–17099, 1996

    Article  PubMed  CAS  Google Scholar 

  15. Fryer HJ, Davis GE, Manthorpe M, Varon S: Lowry protein assay using an automatic microtiter plate spectrophotometer. Anal Biochem 153(2):262–266, 1986

    Article  PubMed  CAS  Google Scholar 

  16. Shen H, Huang GJ, Gong YW: Effect of transforming growth factor beta and bone morphogenetic proteins on rat hepatic stellate cell proliferation and trans-differentiation. World J Gastroenterol 9(4):784–787, 2003

    PubMed  CAS  Google Scholar 

  17. Sobhonslidsuk A, Roongpisuthipong C, Nantiruj K, et al. : Impact of liver cirrhosis on nutritional and immunological status. J Med Assoc Thai 84(7):982–988, 2001

    PubMed  CAS  Google Scholar 

  18. Triger DR, Wright R: Hyperglobulinaemia in liver disease. Lancet 1(7818):1494–1496, 1973

    Article  PubMed  CAS  Google Scholar 

  19. Husby G, Skrede S, Blomhoff JP, Jacobsen CD, Berg K, Gjone E: Serum immunoglobulins and organ non-specific antibodies in diseases of the liver. Scand J Gastroenterol 12(3):297–304, 1977

    Article  PubMed  CAS  Google Scholar 

  20. Revillard JP, Millet I: Fc receptor-bearing T cells and Ig binding factors as class-specific suppressors of polyclonally activated human B cells. Int Rev Immunol 2(2):183–201, 1987

    Article  PubMed  CAS  Google Scholar 

  21. Kijimoto-Ochiai S, Uede T: CD23 molecule acts as a galactose-binding lectin in the cell aggregation of EBV-transformed human B-cell lines. Glycobiology 5(4):443–448, 1995

    Article  PubMed  CAS  Google Scholar 

  22. Bajorath J, Aruffo A: Structure-based modeling of the ligand binding domain of the human cell surface receptor CD23 and comparison of two independently derived molecular models. Protein Sci 5(2):240–247, 1996

    Article  PubMed  CAS  Google Scholar 

  23. Leach JL, Sedmak DD, Osborne JM, Rahill B, Lairmore MD, Anderson CL: Isolation from human placenta of the IgG transporter, FcRn, and localization to the syncytiotrophoblast: implications for maternal-fetal antibody transport. J Immunol 157(8):3317–3322, 1996

    PubMed  CAS  Google Scholar 

  24. Dickinson BL, Badizadegan K, Wu Z, et al. : Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J Clin Invest 104(7):903–911, 1999

    Article  PubMed  CAS  Google Scholar 

  25. Masuda M, Roos D: Association of all three types of Fc gamma R (CD64, CD32, and CD16) with a gamma-chain homodimer in cultured human monocytes. J Immunol 151(12):7188–7195, 1993

    PubMed  CAS  Google Scholar 

  26. Hulett MD, Hogarth PM: The second and third extracellular domains of FcgammaRI (CD64) confer the unique high affinity binding of IgG2a. Mol Immunol 35(14–15):989–996, 1998

    Article  PubMed  CAS  Google Scholar 

  27. van Vugt MJ, Kleijmeer MJ, Keler T, et al. : The FcgammaRIa (CD64) ligand binding chain triggers major histocompatibility complex class II antigen presentation independently of its associated FcR gamma-chain. Blood 94(2):808–817, 1999

    PubMed  CAS  Google Scholar 

  28. Edberg JC, Moon JJ, Chang DJ, Kimberly RP: Differential regulation of human neutrophil FcgammaRIIa (CD32) and FcgammaRIIIb (CD16)-induced Ca$^{2+}$ transients. J Biol Chem 273(14):8071–8079, 1998

    Article  PubMed  CAS  Google Scholar 

  29. Tosi MF, Zakem H: Surface expression of Fc gamma receptor III (CD16) on chemoattractant-stimulated neutrophils is determined by both surface shedding and translocation from intracellular storage compartments. J Clin Invest 90(2):462–470, 1992

    Article  PubMed  CAS  Google Scholar 

  30. Engelhardt W, Matzke J, Schmidt RE: Activation-dependent expression of low affinity IgG receptors Fc gamma RII(CD32) and Fc gamma RIII(CD16) in subpopulations of human T lymphocytes. Immunobiology 192(5):297–320, 1995

    PubMed  CAS  Google Scholar 

  31. Carosella ED, Gay C, Armand J, Touraine JL: Human B-cell differentiation by Fc fragment of IgG. I. Fc fragment from human IgG induces plasma cell generation but cannot induce lymphocyte proliferation. Cell Immunol 112(2):262–270, 1988

    CAS  Google Scholar 

  32. Uher F, Lamers MC, Dickler HB: Antigen-antibody complexes bound to B-lymphocyte Fc gamma receptors regulate B-lymphocyte differentiation. Cell Immunol 95(2):368–379, 1985

    Article  PubMed  CAS  Google Scholar 

  33. Berman MA, Weigle WO: B-lymphocytes activation by the Fc region of IgG. J Exp Med 146(1):241–256, 1977

    Article  PubMed  CAS  Google Scholar 

  34. Moore RW, Caldwell DY, Berghman LR, et al. : Effect of bursal anti-steroidogenic peptide and immunoglobulin G on neonatal chicken B-lymphocyte proliferation. Comp Biochem Physiol C Toxicol Pharmacol 134(3):291–302, 2003

    Article  PubMed  CAS  Google Scholar 

  35. Bijsterbosch MK, McLaughlin JB, Holman M, Klaus GG. Activation and proliferation signals in mouse B cells. IX. Protein kinase C activators synergize with non-mitogenic anti-immunoglobulin antibodies to drive B cells into G1. Immunology 64(1):163–168, 1988

    PubMed  CAS  Google Scholar 

  36. Michaelsen TE, Wisloff F, Natvig JB: Structural requirements in the Fc region of rabbit IgG antibodies necessary to induce cytotoxicity by human lymphocytes. Scand J Immunol 4(1):71–78, 1975

    Article  PubMed  CAS  Google Scholar 

  37. Nakamura K, Yube K, Miyatake A, Cambier JC, Hirashima M: Involvement of CD4 D3-D4 membrane proximal extracellular domain for the inhibitory effect of oxidative stress on activation-induced CD4 down-regulation and its possible role for T cell activation. Mol Immunol 39(15):909–921, 2003

    Article  PubMed  CAS  Google Scholar 

  38. Metes D, Manciulea M, Pretrusca D, et al. : Ligand binding specificities and signal transduction pathways of Fc gamma receptor IIc isoforms: the CD32 isoforms expressed by human NK cells. Eur J Immunol 29(9):2842–2852, 1999

    Article  PubMed  CAS  Google Scholar 

  39. Hardwick JS, Sefton BM: Activation of the Lck tyrosine protein kinase by hydrogen peroxide requires the phosphorylation of Tyr-394. Proc Natl Acad Sci USA 92(10):4527–4531, 1995

    Article  PubMed  CAS  Google Scholar 

  40. Franklin RA, McLeod A, Robinson PJ: Calcium-induced p56(Lck) phosphorylation in human T lymphocytes via calmodulin dependent kinase. Biochem Biophys Res Commun 259(2):283–286, 1999

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada

    Hong Shen & Yuewen Gong

  2. Departments of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

    Hong Shen, Manna Zhang, Kelly Kaita, Gerald Y. Minuk, Julia Rempel & Yuewen Gong

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  1. Hong Shen
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Correspondence to Yuewen Gong.

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Shen, H., Zhang, M., Kaita, K. et al. Expression of Fc Fragment Receptors of Immunoglobulin G (FcγRs) in Rat Hepatic Stellate Cells. Dig Dis Sci 50, 181–187 (2005). https://doi.org/10.1007/s10620-005-1298-5

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  • DOI: https://doi.org/10.1007/s10620-005-1298-5

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