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Heterogeneity of kupffer cells and splenic, alveolar, and peritoneal macrophages for the production of TNF, IL-1, AND IL-6

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Abstract

Kupffer cells and alveolar, splenic, and peritoneal macrophages from normal rats were incubated for various periods of time in the presence of LPS, and the culture supernatants were analyzed for IL-6, IL-1, and TNF. There was very little difference in the amounts of the cytokines produced by the macrophages when stimulated with 0.01–10μ/ml of LPS. The shapes of the time course curves for the production of the cytokines by the different types of macrophages were generally similar, although only Kupffer cells continued to produce IL-6 throughout the entire incubation period and splenic macrophages showed a lag period in the production of IL-1. Kupffer cells produced more IL-6 than that produced by the other populations of macrophages, and alveolar macrophages produced more IL-1 compared to that produced by splenic cells. Kupffer cells and peritoneal macrophages produced more IL-6 in 24 h than in 6 h of culture, and splenic macrophages produced more IL-1 in 24 compared to 6 h of culture. Alveolar macrophages produced more TNF than that produced by the other populations of cells but only when integrated over the entire incubation period. These results confirm and extend the observed functional heterogeneity of macrophages obtained from different tissues of the same animal. This study and future studies will lead to a better understanding of the role of cytokines in the inflammatory response.

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References

  1. Rutherford, M. S., A. Witsell, andL. B. Schook. 1993. Mechanisms generating functionally heterogeneous macrophage: Chaos revisitedJ. Leukocyte Biol. 53:602–618.

    PubMed  Google Scholar 

  2. Adams, D. O., andT. J. Koerner. 1989. Gene regulation in macrophage development and activation.In The Year in Immunology. Cellular, Molecular, and Clinical Aspects, J. M. Cruse, and R. E. Lewis, Jr., editors. Karger, Basel, Switzerland. 159.

    Google Scholar 

  3. Shieh, J.-H., R. H. F. Peterson andM. A. S. Moore. 1994. Bacterial endotoxin regulation of cytokine receptors on murine bone marrow cells: In vivo and in vitro study.J. Immunol. 152:860–866.

    Google Scholar 

  4. Waage, A., A. Halstensen, R. Shalaby, P. Brandtzaeg, P. Kierulf, andT. Espevik. 1989. Local production of tumor necrosis factorα, interleukin 1, and interleukin 6 in meningococcal meningitis.J. Exp. Med. 170:1859–1867.

    PubMed  Google Scholar 

  5. Walker, W. S. 1989. Differential antigen presentation by cloned populations of mouse splenic macrophages.J. Immunol. 143:2142–2145.

    PubMed  Google Scholar 

  6. Khansari, N., Y. K. Chow, andH. H. Fudenberg. 1985. Human monocyte heterogeneity: Interleukin a and prostaglandin E2 production by separate subsets.Eur. J. Immunol. 15:48–51.

    PubMed  Google Scholar 

  7. Sorg, C. 1982. Heterogeneity of macrophages in response to lymphokines and other signals.Mol. Immunol. 19:1275–1278.

    PubMed  Google Scholar 

  8. Meyers, M. J., J. K. Pullen, N. Ghildyal, E. Eustis-Turn andL. B. Schook. 1989. Regulation of IL-1 and TNF-α expression during the differentiation of bone marrow-derived macrophages.J. Immunol. 142:153–160.

    PubMed  Google Scholar 

  9. Pullen, J. K., E. Eustis-Turf, M. J. Myers, andL. B. Schook. 1989. Regulation of MHC gene expression during the differentiation of bone marrow-derived macrophages.Cell. Immunol. 121:398–413.

    PubMed  Google Scholar 

  10. Geng, Y., B. Zhang, andM. Lotz. 1993. Protein tyrosine kinase activation is required for lipopolysaccharide induction of cytokines in human blood monocytes.J. Immunol. 151:6692–6700.

    PubMed  Google Scholar 

  11. Cavaillon, J. M., andN. Haeffner-Cavaillon. 1990. Signals involved in interleukin 1 synthesis and release by lipopolysaccharide-stimulated monocytes/macrophages.Cytokine 2:313–329.

    PubMed  Google Scholar 

  12. Trinchieri, G. 1991. Regulation of tumor necrosis factor production by monocyte-macrophages and lymphocytes.Immunol. Res. 10:89–103.

    PubMed  Google Scholar 

  13. Goldfeld, A. E., C. Doyle, andT. Maniatis. 1990. Human tumor necrosis factor alpha gene regulation by virus and lipopolysaccharide.Proc. Natl. Acad. Sci. U.S.A. 87:9769–9773.

    PubMed  Google Scholar 

  14. Libermann, T. A., andD. Baltimore. 1990. Activation of interleukin-6 gene expression through the NF-kappa B transcription factor.Mol. Cell Biol. 10:2327–2334.

    PubMed  Google Scholar 

  15. Beutler, B., andA. Cerami. 1989. The biology of cachectin/TNF- primary mediator of the host response.Annu. Rev. Immunol. 7:625–655.

    PubMed  Google Scholar 

  16. Dinarello, C. A. 1989. Interleukin-1 and its biologically related cytokines.Adv. Immunol. 44:153–205.

    PubMed  Google Scholar 

  17. Ramadori, G., J. Van Damme, H. Reider, andK. H. Meyer. 1988. Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1 beta and tumor necrosis factor-alpha.Eur. J. Immunol. 18:1259–1264.

    PubMed  Google Scholar 

  18. Vincenti, M. P., T. A. Burrell, andS. M. Taffet. 1992. Regulation of NF-kappa B activity in murine macrophages: Effect of bacterial lipopolysaccharide and phorbol ester.J. Cell Physiol. 150:204–213.

    PubMed  Google Scholar 

  19. Mackman, N., K. Brand, andT. S. Edgington. 1991. Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in THP-a monocytic cells requires both activator protein 1 and nuclear factor kappa B binding sites.J. Exp. Med. 174:1517–1526.

    PubMed  Google Scholar 

  20. Lei, M. G., andD. C. Morrison. 1988. Specific endotoxic lipopolysaccharide-binding proteins on murine splenocytes: I. Detection of lipopolysaccharide-binding sites on splenocytes and splenocyte subpopulations.J. Immunol. 141:996–1005.

    PubMed  Google Scholar 

  21. Shakhov, A. N., M. A. Collart, P. Vasalli, S. A. Nedospasov, andC. V. Jongeneel. 1990. Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages.J. Exp. Med. 171:35–47.

    PubMed  Google Scholar 

  22. Waage, A., A. Halstensen, R. Shalaby, P. Brandtzaeg, P. Kierulf andT. Espevik. 1989. Local production of tumor necrosis factor alpha, interleukin 1, and inflammatory response.J. Exp. Med. 170:1859–1867.

    PubMed  Google Scholar 

  23. Girardin, E., G. E. Grau, J. M. Dayer, P. Roux-Lombard, andP. H. Lambert. 1988. Tumor necrosis factor and interleukin-1 in the serum of children with sever infectious purpura.N. Engl. J. Med. 319:397–400.

    PubMed  Google Scholar 

  24. Waage, A., P. Brandtzaeg, A. Halstensen, P. Kierulf, andT. Espevik. 1989. The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome.J. Exp. Med. 169:333–338.

    PubMed  Google Scholar 

  25. Ouwendijk, R. J. T., F. J. Aijilstra, A. M. W. C. Van den Broek, A. Brouwer, J. H. P. Wilson, andJ. E. Vincent. 1988. Comparison of the production of eicosanoids by human and rat peritoneal macrophages and rat Kupffer cells.Prostaglandins 35:437–446.

    PubMed  Google Scholar 

  26. Ogle, C. K., J. D. Ogle, C. Johnson, L. Keynton, andJ. W. Alexander. 1988. The production of C3, PGE2., and TxB2 by splenic, alveolar and peritoneal guinea pig macrophages.Prostaglandins 036:279–289.

    PubMed  Google Scholar 

  27. Tachibana, K., G.-J. Chen, D. S. Huang, P. Scuderi, andR. R. Watson. 1992. Production of tumor necrosis factorα by resident and activated murine macrophages.J. Leukocyte Biol. 51:251–255.

    PubMed  Google Scholar 

  28. Becker, S., R. B. Devlin, andJ. S. Haskill. 1989. Differential production of tumor necrosis factor, macrophage colony stimulating factor, and interleukin 1 by human alveolar macrophages.J. Leukocyte Biol. 45:353–361.

    PubMed  Google Scholar 

  29. Wu, J. Z., C. K. Ogle, J. D. Ogle, andJ. W. Alexander. 1993. A comparison of hepatic, splenic, peritoneal and alveolar macrophages with respect to PGE2, TxB2, production and ADCC function.Prostaglandins Leukotrienes Essent. Fatty Acids 48:149–153.

    Google Scholar 

  30. Shacter, E., G. K. Arzadon, andJ. Williams. 1992. Elevation of interleukin-6 in response to a chronic inflammation stimulus in mice: Inhibition by indomethacin.Blood 80:194–202.

    PubMed  Google Scholar 

  31. Aarden, L. A., E. R. DeGroot, O. L. Schaap, andP. M. Lansdorp. 1987. Production of hybridoma growth factor by human monocytes.Eur. J. Immunol. 17:1411–1416.

    PubMed  Google Scholar 

  32. Ruff, M. R., and G. E.Gifford. Tumor necrosis factor.In Lymphokines, Vol. 2. E. Pick, editor. Academic Press, New York. 235–273.

  33. Gerrard, T. L., J. P. Siegel, D. R. Dyer, andK. C. Zoon. 1987. Differential effects of interferon-α and interferon-γ on interleukin 1 secretion by monocytes.J. Immunol. 138:2535–2540.

    PubMed  Google Scholar 

  34. Imamura, K., D. Spriggs andD. Kufe. 1987. Expression of tumor necrosis factor receptors on human monocytes and internalization of receptor bound ligand.J. Immunol. 139:2989–2992.

    PubMed  Google Scholar 

  35. Falk, L. A., M. M. Hogan, andS. N. Vogel. 1988. Bone narrow progenitors cultured in the presence of granulocyte-macrophage colony-stimulating factor versus macrophage colony-stimulating factor differentiate into macrophages with distinct tumoricidal capacities.J. Leukocyte Biol. 43:471–476.

    PubMed  Google Scholar 

  36. Drost, A. C., D. G. Burleson, W. G. Cioffi, B. S. Jordan, A. D. Mason, Jr., andB. A. Pruitt, Jr. 1993. Plasma cytokines following thermal injury and their relationship with patient mortality, burn size, and time postburn.J. Trauma 35:335–339.

    PubMed  Google Scholar 

  37. Fong, Y., K. J. Tracey, L. L. Moldawer, D. G. Hesse, K. B. Monoque, J. S. Kenney, A. T. Lee, G. C. Kuo, A. C. Allison, andS. F. Lowry. 1989. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1β and interleukin 6 appearance during lethal bacteremia.Exp. Med. 170:1627–1633.

    Google Scholar 

  38. O'Neill, P. J., A. Ayala, P., Wang, F. B. Zheng, M. H. Morrison, A. E. Schultze, S. S. Reich, andI. H. Chaudry. 1994. Role of kupffer cells in interleukin-6 release following trauma-hemorrhage and resuscitation.Shock 1:43–47.

    PubMed  Google Scholar 

  39. Wewers, M. D., andD. J. Herzyk. 1989. Alveolar macrophages differ from blood monocytes in human IL-1β release.J. Immunol. 143:1635–1641.

    PubMed  Google Scholar 

  40. Herzyk, D. J., J. N. Allen, C. B. Marsh, andM. D. Wewers. 1992. Macrophage and monocyte IL-1β regulation differs at multiple sites. Messenger RNA expression, translation, and post-translational processing.J. Immunol. 149:3052–3058.

    PubMed  Google Scholar 

  41. Fukushima, R., J. W. Alexander, L. Gianotti, andC. Ogle. 1994. The lung as a major source of systemic TNF.Crit. Care Med. 22:114–128.

    PubMed  Google Scholar 

  42. Colotta, F., N. Polentarutti, L. Bersani, G. Poli, andA. Mantovani. 1986. Rapid killing of actinomycin D-treated tumor cells by mononuclear phagocytes: Characterization of effector cells in mice.J. Leukocyte Biol. 39:205–221.

    PubMed  Google Scholar 

  43. Tachibana, K., G. Chen, D. S. Huang, P. Scuderi, andR. R. Watson. 1992. Production of tumor necrosis factorα by resident and activated murine macrophages.J. Leukocyte Biol. 51:251–255.

    PubMed  Google Scholar 

  44. Becker, S., R. B. Devlin, andJ. S. Haskill. 1989. Differential production of tumor necrosis factor, macrophage colony-stimulating factor, and interleukin 1 by human alveolar macrophages.J. Leukocyte Biol. 45:353–361.

    PubMed  Google Scholar 

  45. Decker, T., M.-L. Lohmann-Matthes, andG. E. Gifford. 1987. Cell-associated tumor necrosis factor (TNF) as a killing mechanism of activated cytotoxic macrophages.J. Immunol. 138:957–962.

    PubMed  Google Scholar 

  46. Parhar, R. S., andP. K. Lala. 1988. Prostaglandin E2-mediated inactivation of various killer lineage cells by tumor-bearing host macrophages.J. Leukocyte Biol. 44:474–484.

    PubMed  Google Scholar 

  47. Chensue, S. W., C. Shmyr-Forsch, A. Weng, I. G. Otterness, andS. L. Kunkel. 1989. Biologic and immunohistochemical analysis of macrophage interleukin-1α, -1β, and tumor necrosis factor production during the peritoneal exudative responseJ. Leukocyte Biol. 46:529–537.

    PubMed  Google Scholar 

  48. Beuscher, H. U., U.-P. Rausch, I. G. Otterness, andM. Rollinghoff. 1992. Transition from interleukin 1β (IL-1β) to IL-1α production during maturation of inflammatory macrophages in vivo.J. Exp. Med. 175:1793–1797.

    PubMed  Google Scholar 

  49. Mielke, M. E. A., H. Rosen, S. Brocke, andH. Hahn. 1992. Protective immunity and granuloma formation are mediated by two distinct tumor necrosis factor alpha- and gamma interferon-dependent T cell-phagocyte interactions in murine listeriosis: Dissociation on the basis of phagocyte adhesion mechanisms.Infect. Immun. 60:1875–1882.

    PubMed  Google Scholar 

  50. Scales, W. E., S. W. Chensue, I. Otterness, andS. L. Kunkel. 1989. Regulation of monokine gene expression: Prostaglandin E2 suppresses tumor necrosis factor but not interleukin-1α orβ-mRNA and cell-associated bioactivity.J. Leukocyte Biol. 45:416–421.

    PubMed  Google Scholar 

  51. Rutherford, M. S., andL. B. Schook. 1992. Macrophage function in response to PGE2,l-arginine deprivation, and activation by colony-stimulating factors is dependent on hematopoietic stimulus.J. Leukocyte Biol. 52:228–235.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, University of Cincinnati Medical Center, 45267, Cincinnati, Ohio

    Cora K. Ogle & J. Wesley Alexander

  2. Cincinnati Unit, Shriners Burns Institute, 45229, Cincinnati, Ohio

    Cora K. Ogle, Jun-Zhen Wu, Xialing Mao, Kathy Szczur, J. Wesley Alexander & James D. Ogle

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Ogle, C.K., Wu, JZ., Mao, X. et al. Heterogeneity of kupffer cells and splenic, alveolar, and peritoneal macrophages for the production of TNF, IL-1, AND IL-6. Inflammation 18, 511–523 (1994). https://doi.org/10.1007/BF01560698

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