Skip to main content
Log in

Effect of alpha-2-macroglobulin on cytokine-mediated human C-reactive protein production

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Alpha-2-macroglobulin (α2-M), a serum protease inhibitor that also binds cytokines, neutralized the inhibitory effect exerted by transforming growth factor-Β (TGF-Β) on IL-6-induced C-reactive protein (CRP) production by the human hepatoma cell line PLC/PRF/5. α2-M was found to bind noncovalently with TGF-Β to form a complex that, upon acidification, released TGF-Β inhibitory activity as detected by IL-6-induced CRP production. Although α2-M also binds IL-6, it did not alter IL-6-induced CRP production by the hepatoma cells. The interaction between α2-M and TGF-Β may influence the production of acute-phase proteins by liver hepatocytes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gordon, A. H., andA. Koj. 1985.Acute Phase Response to Injury and Infection, Elsevier, Amsterdam.

    Google Scholar 

  2. Kushner, I. 1982. The phenomenon of the acute phase response.Ann. N. Y. Acad. Sci. 389:39.

    Google Scholar 

  3. Pepys, M. B., andM. L. Baltz. 1983. Acute phase proteins with special reference to C-reactive protein and related proteins (pentraxins) and serum amyloid A protein.Adv. Immunol. 34:141.

    Google Scholar 

  4. Balkwill, F. R., andF. Burke. 1989. The cytokine network.Immunol. Today 10:299.

    Google Scholar 

  5. Wong, G. C., andS. C. Clark. 1988. Multiple actions of IL-6 within a cytokine network.Immunol. Today 9:137.

    Google Scholar 

  6. Darlington, G. J., D. R. Wilson, andL. B. Lachman. 1986. Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hematoma cellsin vitro.J. Cell Biol. 103:787.

    Google Scholar 

  7. Goldman, N. D., andT.-Y. Liu. 1987. Biosynthesis of human C-reactive protein in cultured hepatoma cells in induced by a monocyte factor(s) other than interleukin-1.J. Biol. Chem. 262:2363.

    Google Scholar 

  8. Ganapathi, M. K., L. T. May, D. Schultz, A. Brabenec, J. Weinstein, P. B. Sehgal, andI. Kushner. 1988. Role of interleukin-6 in regulating synthesis of C-reactive protein and serum amyloid A in human hepatoma cell lines.Biochem. Biophys. Res. Commun. 150:271.

    Google Scholar 

  9. Taylor, A. W., N.-O. Ku, andR. F. Mortensen. 1989. Both human IL-1 and IL-6 induce synthesis of CRP by the PLC/PRF/5 hepatoma cell line.Ann. N. Y. Acad. Sci. 557:532.

    Google Scholar 

  10. Castell, J. V., T. Andus, D. Junz, andP. C. Heinrich. 1989. Interleukin-6: The major regulator of acute-phase protein synthesis in man and rat.Ann. N.Y. Acad. Sci. 557:87.

    Google Scholar 

  11. Moshage, H. J., H. M. J. Roelofs, J. F. Van Pelt, B. P. C. Hayenberg, M. A. Van Leeuwen, P. C. Limburg, L. A. Aarden, S. H. Yap. 1988. The effect of IL-1, IL-6 and its interrelationship on the synthesis of serum amyloid A and C-reactive protein in primary cultures of adult human hepatocytes.Biochem. Biophys. Res. Commun. 155:112.

    Google Scholar 

  12. Baumann, H. 1989. Hepatic acute phase reactionin vivo andin vitro.In Vitro Cell. Dev. Biol. 25:115.

    Google Scholar 

  13. Ganter, U., R. Arcone, C. Toniatti, G. Morrone, andG. Ciliberto. 1989. Dual control of C-reactive protein gene expression by interleukin-1 and interleukin-6.EMBO J. 8:3773.

    Google Scholar 

  14. Gewurz, H., C. Mold, J. Siegel, andB. Fiedel. 1982. C-reactive protein and the acute phase response.Adv. Intern. Med. 27:345.

    Google Scholar 

  15. Schreiber, G., A. Tsykin, A. R. Aldred, T. Thomas, W.-P. Pong, P. W. Dickson, T. Cole, H. Birch, F. A. DeJong, andJ. Milland. 1989. The acute phase response in the rodent.Ann. N.Y. Acad. Sci. 557:61.

    Google Scholar 

  16. Feldman, S. R., S. L. Gonias, andS. V. Pizzo. 1985. Model ofα2-M-macroglobulin structure and function.Proc. Natl. Acad. Sci. U.S.A. 82:5700.

    Google Scholar 

  17. Sottrup-Jensen, L. 1989.α-Macroglobulins: Structure, shape, and mechanism of proteinase complex formation.J. Biol. Chem. 264:11539.

    Google Scholar 

  18. Arakawa, H., M. Nishigai, andA. Ikai. 1989.α2-Macroglobulin traps a proteinase in the midregion of its arms.J. Biol. Chem. 264:2350.

    Google Scholar 

  19. O'Connor-McCourt, M. D., andL. M. Wakefield. 1987. Latent transforming growth factor-Β in serum: A specific complex withα 2-macroglobulin.J. Biol. Chem. 262:14090.

    Google Scholar 

  20. Matsuda, T., T. Hirano, S. Nagasawa, andT. Kishimoto. 1989. Identification ofα2-macroglobulin as a carrier protein for IL-6.J. Immunol. 142:148.

    Google Scholar 

  21. Borth, W., andT. A. Luger. 1988. Identification of aα2-macroglobulin as a cytokine binding plasma protein.J. Biol. Chem. 264:5518.

    Google Scholar 

  22. James, K. 1990. Interactions between cytokines andα2-macroglobulin.Immunol. Today 11:163.

    Google Scholar 

  23. Wahl, S. M., N. McCartney-Francis, andŚ. E. Mergenhagen. 1989. Inflammatory and immunomodulatory roles of TGF-Β.Immunol. Today 10:258.

    Google Scholar 

  24. Danielpour, D., andM. B. Sporn. 1990. Differential inhibition of transforming growth factorΒ 1 andΒ2 activity byα2-macroglobulin.J. Biol. Chem. 265:6973.

    Google Scholar 

  25. Wakefield, L. M., D. M. Smith, K. C. Flanders, andM. B. Sporn. 1988. Latent transforming growth factor-Β from human platelets.J. Biol. Chem. 263:7646.

    Google Scholar 

  26. Taylor, A. W., N.-O. Ku, andR. F. Mortensen. 1990. Regulation of cytokine-induced human C-reactive protein production by transforming growth factor-Β.J. Immunol. 145:2507.

    Google Scholar 

  27. Aden, D. P., A. Fogel, S. Plotkin, I. Domjanov, andB. B. Knowles. 1979. Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line.Nature 282:615.

    Google Scholar 

  28. May, L. T., D. C. Helfgott, andP. B. Sehgal. 1986. Anti-Β-interferon antibodies inhibit the increased expression of HLA-B7-mRNA in tumor necrosis factor treated fibroblasts of theΒ 2-interferon involved.Proc. Natl. Acad. Sci. U.S.A. 83:8957.

    Google Scholar 

  29. Wong, G. G., G. S. Witek-Giannotti, P. A. Temple, R. Kriz, C. Ferenz, R. M. Hewick, S. C. Clark, K. Ikebuchi, andM. Ogawa. 1988. Stimulation of murine hemopoietic colony formation by human IL-6.J. Immunol. 140:3040.

    Google Scholar 

  30. Derynck, R., J. A. Jarett, E. Y. Chen, D. H. Eaton, J. R. Bell, R. I. K. Assoian, A. B. Roberts, M. B. Sporn, andD. V. Goeddel. 1985. Human transforming growth factor-Β complementary DNA sequence and expression in normal and transformed cells.Nature 316:701.

    Google Scholar 

  31. Zahedi, K., J. M. Tebo, J. Siripont, G. F. Klimo, andR. F. Mortensen. 1988. Binding of human C-reactive protein to mouse macrophages is mediated by distinct receptors.J. Immunol. 142:2384.

    Google Scholar 

  32. Roberts, A. B., andM. B. Sporn. 1988. Transforming growth factor-Β.Adv. Cancer Res. 51:107.

    Google Scholar 

  33. Twardzik, D. R., J. A. Mikovits, J. E. Ranchalis, A. F. Purchio, L. Ellingsworth, andF. W. Ruscetti. 1990. γ-Interferon-induced activation of latent transforming growth factor-Β by human monocytes.Ann. N.Y. Acad. Sci. 593:276.

    Google Scholar 

  34. Debanne, M. T., R. Bell, ANDJ. Dolovich. 1976. Characteristics of the macrophage uptake of proteinase-2-macroglobulin complexes.Biochim. Biophys. Acta 428:466.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taylor, A.W., Mortensen, R.F. Effect of alpha-2-macroglobulin on cytokine-mediated human C-reactive protein production. Inflammation 15, 61–70 (1991). https://doi.org/10.1007/BF00917910

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00917910

Keywords

Navigation