Skip to main content
Log in

α 2Macroglobulin-proteinase complexes stimulate prostaglandin E2 synthesis by peritoneal macrophages

  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

α2Macroglobulin is a proteinase inhibitor which is converted from its native form into an electrophoretically “fast” form by reaction with a proteinase or methylamine. All α2M “fast” forms bind to a specific high-affinity receptor on macrophages. α2M “fast” forms inhibit the interferon-γ (IFN)-induced increase in macrophage Ia expression. This study examined whether α2M-proteinase complexes alter prostaglandin (PG) E2 synthesis, and whether PGE2 mediates α2M “fast” forms effects on macrophage Ia expression. Culture with α2M “fast” forms increased PGE2 accumulation in the medium over control values in a dose-dependent manner. Culture with IFN alone did not increase PGE2 levels, but potentiated the effect of α2M-proteinase complexes on PGE2 levels. Inhibition of PGE2 synthesis did not alter the PGE2 did suppress IFN-induced Ia expression. Thus, α2M-proteinase complexes increase macrophage PGE2 synthesis, but increased synthesis of PGE2 or other cyclooxygenase products is not the mediator of antagonism of IFN-induced Ia expression by α2M-proteinase complexes.

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.

Similar content being viewed by others

References

  1. A. J. Barrett,α 2-Macroglobulin. Meth. Enzymol. 80, 737–754 (1981).

    PubMed  Google Scholar 

  2. P. O. Ganrot, Determination of α2-macroglobulin as trypsin-protein esterase. Clin. Chim. Acta14, 493–501 (1966).

    Google Scholar 

  3. S. R. Feldmann, K. A. Ney, S. L. Gonias and S. V. Pizzo, In vitro binding and in vivo clearance of human α2-macroglobulin after reaction with endopeptidases from four different classes. Biochem. Biophys. Res. Commun.114, 757–762 (1983).

    PubMed  Google Scholar 

  4. W. J. Johnson, S. V. Pizzo, M. J. Imber and D. O. Acams,Receptors for maleylated proteins regulate secretion of neutral proteases by murine macrophages. Science218, 574–576 (1982).

    PubMed  Google Scholar 

  5. M. Hoffman, S. Feldman and S. Pizzo α2-macroglobulin “fast” forms inhibit superioxide production by activated macrophages. Biochim. Biophys. Acta760, 421–423 (1983).

    PubMed  Google Scholar 

  6. M. Hoffman, S. V. Pizzo and J. B. Weinberg, Modulation of mouse peritoneal macrophage Ia and human peritoneal macrophage HLA-DR expression by α2-macroglobulin “fast” forms. J. Immunol.139, 1885–1890 (1987).

    PubMed  Google Scholar 

  7. J. Niederhuber,The role of I region gene products in macrophage-T lymphocyte interactions. Immunol. Rev.40, 38–56 (1978).

    Google Scholar 

  8. S. L. Kunkel and S. W. Chensue,Prostaglandins and the Regulation of Immune Responses. Adv. Inflamm. Res.7, 93–107 (1984).

    Google Scholar 

  9. T. S. Rogers, E. F. Smith III, W. C. Wise, P. V. Halushka and J. A. Cook,Interaction of Eicosanoids and Macrophages during Inflammatory Responses. Surv. Immunol. Res.3, 161–164 (1984).

    PubMed  Google Scholar 

  10. P. S. Steeg, H. M. Johnson and J. J. Oppenheim,Regulation of murine macrophage Ia antigen expression by an immune interferonlike lymphokine: Inhibitory effect of endotoxin. J. Immunol.129, 2402–2406 (1982).

    PubMed  Google Scholar 

  11. S. L. Kunkel, D. A. Campbell Jr, S. W. Chensue and G. I. Higashi,Species-dependent regulation of monocyte/macrophage Ia antigen expression and antigen presentation by prostaglandin E. Cellular Immunol.97, 140–145 (1986).

    Google Scholar 

  12. S. R. Brandwein,Regulation of Interleukin 1 Production by Mouse Peritoneal Macrophages. Effects of arachidonic acid metabolites, cyclic nucleotides, and interferons. J. Biol. Chem.261, 8624–8632 (1986).

    PubMed  Google Scholar 

  13. S. L. Kunkel, R. C. Wiggins, S. W. Chensue and J. Larrick,Regulation of macrophage tumor necrosis factor production by prostaglandin E 2. Biochem. Biophys. Res. Commun.137, 404–410 (1986).

    PubMed  Google Scholar 

  14. R. G. Sitrin, H. B. Kaltreider and M. E. Goldyne,Prostaglandin E is required for the augmentation of procoagulant activity of LPS-stimulated rabbit alveolar macrophages. J. Immunol.132, 867–871 (1984).

    PubMed  Google Scholar 

  15. R. J. Bonney, S. Burger, P. Davies, F. A. Kuehl and J. L. Humes,Prostaglandin E 2 and prostacyclin elevate cyclic AMP levles in elcited populations of mouse peritoneal macrophages. InAdvances in Prostagladin and Thromboxane Research, vol. 3. (Ed. B. Samuelsson, P. W. Ramwell and R. Paoletti). pp. 1691–1693, Raven Press, New York 1980.

    Google Scholar 

  16. T. Kurecki, L. F. Kress and M. Laskowski, Sr,Purification of human alpha 2-macroglobulin and alpha 1-proteinase inhibitor using zinc chelate chromatography. Anal. Biochem.99, 415–420 (1979).

    PubMed  Google Scholar 

  17. M. J. Imber and S. V. Pizzo,Clearance and binding of two electrophoretically “fast” forms of human α2-macroglobulin. J. Biol. Chem.256, 3134–3139 (1981).

    Google Scholar 

  18. P. K. Hall and R. C. Roberts,Physical and chemical properties of human plasma alpha-2-macroglobulin. Biochem. J.173, 27–38 (1978).

    PubMed  Google Scholar 

  19. D. Boraschi, S. Censini and A. Tagliabue,Interferon-γ reduces macrophage-suppressive activity by inhibiting prostaglandin E2 release and inducing interleukin 1 production. J. Immunol.133, 764–768 (1984).

    PubMed  Google Scholar 

  20. K. James,Alpha 2 macroglobulin and its possible importance in immune systems. Trends. Biochem. Sci.5, 43–46 (1980).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hoffman, M., Pizzo, S.V. & Weinberg, J.B. α 2Macroglobulin-proteinase complexes stimulate prostaglandin E2 synthesis by peritoneal macrophages. Agents and Actions 25, 360–367 (1988). https://doi.org/10.1007/BF01965043

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01965043

Keywords

Navigation