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Development of antitumor activity in LPS-stimulated mouse granuloma macrophages

Regulation by eicosanoids

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Abstract

Macrophage-mediated antitumor activity is believed to be regulated by E-type prostaglandins released by target cells or even by macrophages themselves. In these studies we showed that a subcutaneous injection of polyacrylamide beads (Biogel P100), induced in mice, a population of immature macrophages which became fully cytostatic to syngeneic P815 mastocytoma when pulsed in vitro with lipopolysaccharide (LPS). Blockade of prostaglandin synthesis by indomethacin prevented LPS effect and led to a substantial resumption of target growth. Addition of PGE2 did not reverse the indomethacin effect but inhibited macrophage-mediated cytostatic activity. These findings suggest that acquisition of cytostatic properties by macrophages is, at a certain stage of their maturation, under the control of both PGE2 and another endogenously produced eicosanoid.

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References

  1. Schultz, R. M., N. A. Pavlidis, W. A. Stylos, andM. A. Chirigos. 1978. Regulation of macrophage tumoricidal function: A role for prostaglandins of the E series.Science 202:320–321.

    Google Scholar 

  2. Moore, R. N., R. Urbaschek, L. M. Wahl, andS. E. Mergenhagen. 1979. Prostaglandin regulation of colony-stimulating factor. Production by lipopolysaccharide-stimulated murine leukocytes.Infect. Immun. 26:408–414.

    Google Scholar 

  3. Snyder, D. S., D. I. Beller, andE. R. Unanue. 1982. Prostaglandins modulate macrophage Ia expression.Nature 299:163–165.

    Google Scholar 

  4. Hibbs, J. B., Jr., R. R. Taintor, H. A. Chapman, Jr., andJ. B. Weinberg. 1977. Macrophage tumor killing: Influence of the local environment.Science 197:279–282.

    Google Scholar 

  5. Kurland, J. I., andR. Bockman. 1978. Prostaglandin E production by human blood monocyte and mouse peritoneal macrophages.J. Exp. Med. 147:952–957.

    Google Scholar 

  6. Taffet, S. M. andS. W. Russel. 1981. Macrophage-mediated tumor cell killing: Regulation of expression of cytolytic activity.J. Immunol. 126:424–427.

    Google Scholar 

  7. Drysdale, B. E., andM. S. Shin. 1981. Activation of macrophages for tumor cell cytotoxicity: Identification of indomethacin sensitive and insensitive pathways.J. Immunol. 127:760–765.

    Google Scholar 

  8. McCarthy, M. E. andB. S. Zwilling. 1981. Differential effects of prostaglandins on the antitumor activity of normal and BCG-activated macrophages.Cell Immunol. 60:91–99.

    Google Scholar 

  9. Humes, J. L., S. Burger, M. Galavage, F. A. Kuehl, Jr., P. D. Wightman, M. E. Dahlgren, P. Davis, andR. J. Bonney. 1980. The diminished production of arachidonic acid oxygenation products by elicited mouse peritoneal macrophages: Possible mechanisms.J. Immunol. 124:2110–2116.

    Google Scholar 

  10. Hamilton, J. A. 1981. Regulation of prostaglandin and plasminogen activator production by mouse peritoneal macrophages.J. Reticuloendothel. Soc. 30:115–128.

    Google Scholar 

  11. Scott, W. A., N. A. Pawlowski, H. W. Murray, M. Andreach, J. Zrike, andZ. A. Cohn. 1982. Regulation of arachidonic acid metabolism by macrophage activation.J. Exp. Med. 155:1148–1160.

    Google Scholar 

  12. Drapier, J. C., R. Roubin, J. F. Petit, andJ. Benveniste. 1983. Lipid mediator synthesis in peritoneal macrophages from mice injected with immunostimulants.Biochim. Biophys. Acta 751:90–98.

    Google Scholar 

  13. Rouzer, C. A., W. A. Scott, A. L. Hamill, F. T. Liu, D. H. Katz, andZ. A. Cohn. 1982. Secretion of leukotriene C and other arachidonic acid metabolites by macrophages challenged with immunoglobulin E immune complexes.J. Exp. Med. 156:1077–1086.

    Google Scholar 

  14. Beelen, R. H. J., andW. S. Walker. 1983. Dynamics of cytochemically distinct subpopulations of macrophages in elicited rate peritoneal exudates.Cell. Immunol. 82:246–257.

    Google Scholar 

  15. Fauve, R. M., H. Jusforgues, andB. Hevin, 1983. Maintenance of granuloma macrophages in serum-free medium.J. Immunol. Methods 64:345–351.

    Google Scholar 

  16. Miller, G. A. andP. S. Morahan. 1981.In Methods for Studying Mononuclear Phagocytes. D. O. Adams, P. J. Edelson, and H. S. Koren, editors. Academic Press, New York. 367–374.

    Google Scholar 

  17. Lepoivre, M., J. P. Tenu, G. Lemaire, andJ. F. Petit. 1982. Antitumor activity and hydrogen peroxide release by macrophages elicited by trehalose diesters.J. Immunol. 129:860–866.

    Google Scholar 

  18. Lowry, O. H., N. J. Rosenbrough, A. L. Farr, andR. J. Randall. 1951. Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193:265–275.

    Google Scholar 

  19. Drapier, J. C., andJ. F. Petit 1984. Involvement of prostaglandin in LPS-mediated regulation of plasminogen activator synthesis by inflammatory macrophages.Int. J. Immunopharmacol. 6:345–350.

    Google Scholar 

  20. Pick, E., andV. Keisari. 1980. A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture.J. Immunol. Methods 38:161–170.

    Google Scholar 

  21. Humes, J. L., S, Sadowski, M. Galavage, M. Goldenberg, E. Subers, R. J. Bonney, andF. A. Kuehl, Jr. 1982. Evidence for two sources of arachidonic acid foroxidative metabolism by mouse peritoneal macrophages.J. Biol. Chem. 257:1591–1594.

    Google Scholar 

  22. Nathan, C., andZ. A. Cohn. 1980. Role of oxygen-dependent mechanisms in antibodyinduced lysis of tumor cells by activated macrophages.J. Exp. Med. 152:198–208.

    Google Scholar 

  23. Weiss, S. J., A. F. LoBuglio, andH. B. Kessner. 1980. Oxidative mechanisms of monocytemediated cytotoxicity.Proc. Natl. Acad. Sci. U.S.A. 77:584–587.

    Google Scholar 

  24. Mavier, P., andT. S. Edgington. 1984. Human monocyte-mediated tumor cytotoxicity. I. Demonstration of an oxygen-dependent myeloperoxidase-independent mechanism.J. Immunol. 132:1980–1985.

    Google Scholar 

  25. Metzger, Z., J. T. Hoffeld, andJ. J. Oppenheim. 1981. Regulation by PGE2 of the production of oxygen intermediates by LPS-activated macrophages.J. Immunol. 127:1109–1113.

    Google Scholar 

  26. Freedman, V. M., T. E. Gorell, C. F. Nathan, C. S. Copeland, andS. C. Silverstein. 1981. Bacillus Calmette-Guerin-activated murine macrophages kill syngeneic melanoma cells under strict anaerobic conditions.J. Exp. Med. 160:94–107.

    Google Scholar 

  27. Pabst, M. J., andR. B. Johnston, Jr. 1980. Increased production of superoxide anion by macrophages exposed in vitro to muramyl peptide or lipopolysaccharide.J. Exp. Med. 151:101–114.

    Google Scholar 

  28. Cooper, P. K., P. Mayer, andM. Baggiolini. 1984. Stimulation of phagocytosis in bone marrow derived mouse macrophages by bacterial lipopolysaccharide: Correlation with biochemical and functional parameters.J. Immunol. 133:913–922.

    Google Scholar 

  29. Chapes, S. K. andS. Haskill. 1983. Role ofCorynebacterium parvum in the activation of peritoneal macrophages.Cell Immunol. 76:49–57.

    Google Scholar 

  30. Cohen, M. S., S. M. Taffet, andD. O. Adams. 1982. The relationship between competence for secretion of H2O2 and completion of tumor cytotoxicity by BCG-elicited murine macrophages.J. Immunol. 128:1981–1985.

    Google Scholar 

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Drapier, J.C., Petit, J.F. Development of antitumor activity in LPS-stimulated mouse granuloma macrophages. Inflammation 10, 195–204 (1986). https://doi.org/10.1007/BF00916001

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