Proteases II pp 191-198 | Cite as

Induction of the Proteinase Inhibitor α2-Macroglobulin in Rat Hepatocytes by a Monocyte-Derived Factor

  • T. Andus
  • H. Northoff
  • J. Bauer
  • U. Ganter
  • D. Männel
  • T.-A. Tran-Thi
  • K. Decker
  • P. C. Heinrich
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 240)

Abstract

Disturbances of the physiologic homeostasis such as infections, tissue injury, tumor growth and immunologic disorders lead to a highly complex reaction of the organism, the so called acute-phase response1-3. The acute-phase response is characterized by fever, leukocytosis, a negative nitrogen balance, depression of serum iron and zinc levels, elevation of serum copper and dramatic changes in the synthesis of hepatic acute-phase proteins4,5. The plasma concentration of the proteinase inhibator α2-macroglobulin (α2M) or example increases 100-500-fold in the rat during acute inflammation. The concentration of the proteinase-inhibitor α1-inhibitor3 (α1I3) belonging to the same macroglobulin family decreases to about 30% simultaneousely. These changes are generated by mediators secreted from mononuclear phagocytes. Hepatocyte-stimulating factor (HSF), interleukin 1 (IL-1), tumor necrosis factor α (TNFα) and interferon ß (IFN ß) are the most important of theses mediators.

Keywords

Zinc Hydrogen Peroxide Filtration Depression Albumin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    C. A. Dinarello, 1984, Interleukin-1 and the pathogenesis of the acute-phase response, New Engl. J. Med. 1984. 311:1413.PubMedCrossRefGoogle Scholar
  2. 2.
    J. D. Sipe, Cellular and humoral components of the early inflammatory reaction, in: The Acute Phase Response to Injury and Infection, A. Koj, and A.H. Gordon, eds., p. 23, Elsevier, Amsterdam (1985).Google Scholar
  3. 3.
    J. J. Oppenheim, E.J. Kovacs, K. Matsushima, and S.K. Durum, 1986, There is more than one interleukin 1, Immunol. Today 7:45.Google Scholar
  4. 4.
    I. Kushner, 1982, The phenomenon of the acute-phase response, Ann. N. Y. Acad. Sci. 389:39.Google Scholar
  5. 5.
    G. Schreiber, and G. Howlett, in: Plasma Protein Secretion by the Liver, H. Glaumann, T. Peters, and C. Redman, eds., p. 423, Academic Press, London (1983).Google Scholar
  6. 6.
    D. G. Ritchie, B.A. Levy, M.A. Adams, and G.M. Fuller, 1982, Regulation of fibrinogen synthesis by plasmin-derived fragments of fibrinogen and fibrin: An indirect feedback pathway, Proc. Natl. Acad. Sci. USA 79:1530.PubMedCrossRefGoogle Scholar
  7. 7.
    D. G. Ritchie, and G.M. Fuller, 1983, Hepatocyte-stimulating factor: a monocyte-derived acute-phase regulatory protein, Ann. N.Y. Acad. Sci. 408:490.PubMedCrossRefGoogle Scholar
  8. 8.
    J. Bauer, M. Birmelin, G.-H. Northoff, W. Northemann, T.-A. Tran-Thi, H. Ueberberg, K. Decker, and P.C. Heinrich, 1984, Induction of rat α2-macroglobulin in vivo and in hepatocyte primary cultures: synergistic action of glucocorticoids and a Kupffer cell-derived factor, FEBS Lett. 177:89.PubMedCrossRefGoogle Scholar
  9. 9.
    H. Northoff, C. Carter, and J.J. Oppenheim, 1980, Inhibition of concanavalin A-induced human lymphocyte mitogenic factor (interleukin-2). Production by suppressor T-Iymphocytes. J. Immunol. 125:125.Google Scholar
  10. 10.
    C. A. Dinarello, L.J. Rosenwasser, and S.M. Wolff, 1981, Demonstration of a circulating suppressor factor of thymocyte proliferation during endotoxin fever in humans, J. Immunol. 127:2517.Google Scholar
  11. 11.
    E. P. Amento, J. T. Kurnick, and S.M. Krane, 1982, Interleukin-1 production by a human monocyte cell line is induced by a T lymphocyte product, Immunobiology 163:276.CrossRefGoogle Scholar
  12. 12.
    H. Fujiwara, and J.J. Ellner, 1986, Spontaneous production of a suppressor factor by the human macrophage-like cell line U937, J. Immunol. 136:181.PubMedGoogle Scholar
  13. 13.
    M. J. Stadecker, J., Calderon, M.L. Karnovsky, and E.R. Unanue, 1977, Synthesis and release of thymidine by macrophages, J. Immunol. 119:1738.PubMedGoogle Scholar
  14. 14.
    M. Gordon, M.A. Bray, and J. Morley, 1976, Control of lymphokine secretion by prostaglandins, Nature 262:401.PubMedCrossRefGoogle Scholar
  15. 15.
    Z. Metzger, J.T. Hoffeld, and J.J. Oppenheim, 1980, Macrophagemediated suppression. I. Evidence for participation of both hydrogen peroxide and prostaglandins in suppression of murine lymphocyte proliferation. J. Immunol. 124:983.PubMedGoogle Scholar
  16. 16.
    W. Northemann, M. Heisig, D. Kunz, and P.C. Heinrich, 1985, Molecular cloning of cDNA sequences for rat α2-macroglobulin and measurement of its transcription during experimental inflammation. J. Biol. Chem. 260:6200PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • T. Andus
    • 1
  • H. Northoff
    • 2
  • J. Bauer
    • 3
  • U. Ganter
    • 3
  • D. Männel
    • 4
  • T.-A. Tran-Thi
    • 1
  • K. Decker
    • 1
  • P. C. Heinrich
    • 1
  1. 1.Biochemisches InstitutUniv. FreiburgFreiburgGermany
  2. 2.DRK-BlutspendezentraleUlmGermany
  3. 3.Medizinische Univ.-KlinikFreiburgGermany
  4. 4.DKFZ, Institut für ImmunologieHeidelbergGermany

Personalised recommendations