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. 1994 Jan;95(1):115–121. doi: 10.1111/j.1365-2249.1994.tb06024.x

Immune complex-degradation ability of macrophages in MRL/Mp-lpr/lpr lupus mice and its regulation by cytokines.

H Kanno 1, O Tachiwaki 1, M Nose 1, M Kyogoku 1
PMCID: PMC1534628  PMID: 8287594

Abstract

Impaired clearance of circulating and/or deposited immune complexes (IC) by the mononuclear phagocytic system is one of the major factors in the pathogenesis of IC diseases. MRL/Mp-lpr/lpr (MRL/lpr) lupus mice spontaneously develop a lethal glomerulonephritis associated with IC deposition. The ability of macrophages to degrade phagocytozed IC and regulation of this degradation in MRL/lpr mice were examined. In 4-month-old MRL/lpr mice, macrophages accumulated in the affected glomeruli and these macrophages contained many phagosomes containing electron-dense bodies. When culture supernatant of human T cell line HUT102 was administered intraperitoneally into disease-bearing MRL/lpr mice, degradation of these electron-dense bodies in the macrophages in glomeruli was noted. We developed a quantitative in vitro assay for IC degradation activity of MRL/lpr resident peritoneal macrophages (RPM) using peroxidase-labelled IC derived from MRL/lpr mouse sera. The ability of the RPM to degrade IC was remarkably enhanced by the pretreatment with HUT102 cell products and the related human recombinant cytokines, lymphotoxin and IL-1 alpha. Moreover, pretreatment of RPM from non-diseased MRL/Mp-+/+ mice with the culture supernatant of spleen cells from diseased MRL/lpr mice reduced their IC degradation activity. These results suggested that the ability of macrophages to degrade IC in MRL/Mp strains of mice is under the regulation of cytokines, and the impaired ability in the disease-bearing mice may be the result of abnormalities in the cytokine system in these mice.

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Selected References

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  1. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baxter M. A., Leslie R. G., Reeves W. G. The stimulation of superoxide anion production in guinea-pig peritoneal macrophages and neutrophils by phorbol myristate acetate, opsonized zymosan and IgG2-containing soluble immune complexes. Immunology. 1983 Apr;48(4):657–665. [PMC free article] [PubMed] [Google Scholar]
  3. Cheers C., Hill M., Haigh A. M., Stanley E. R. Stimulation of macrophage phagocytic but not bactericidal activity by colony-stimulating factor 1. Infect Immun. 1989 May;57(5):1512–1516. doi: 10.1128/iai.57.5.1512-1516.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Connell P. A., Seehra M. S., Leslie R. G., Reeves W. G. Chemiluminescence of guinea pig peritoneal macrophages stimulated by immune precipitates and soluble immune complexes. Eur J Immunol. 1980 Dec;10(12):966–968. doi: 10.1002/eji.1830101214. [DOI] [PubMed] [Google Scholar]
  5. Dang-Vu A. P., Pisetsky D. S., Weinberg J. B. Functional alterations of macrophages in autoimmune MRL-lpr/lpr mice. J Immunol. 1987 Mar 15;138(6):1757–1761. [PubMed] [Google Scholar]
  6. Frank M. M., Hamburger M. I., Lawley T. J., Kimberly R. P., Plotz P. H. Defective reticuloendothelial system Fc-receptor function in systemic lupus erythematosus. N Engl J Med. 1979 Mar 8;300(10):518–523. doi: 10.1056/NEJM197903083001002. [DOI] [PubMed] [Google Scholar]
  7. Heyman B., Nose M., Weigle W. O. Carbohydrate chains on IgG2b: a requirement for efficient feedback immunosuppression. J Immunol. 1985 Jun;134(6):4018–4023. [PubMed] [Google Scholar]
  8. Ho M. K., Springer T. A. Mac-2, a novel 32,000 Mr mouse macrophage subpopulation-specific antigen defined by monoclonal antibodies. J Immunol. 1982 Mar;128(3):1221–1228. [PubMed] [Google Scholar]
  9. Izui S., Kelley V. E., Masuda K., Yoshida H., Roths J. B., Murphy E. D. Induction of various autoantibodies by mutant gene lpr in several strains of mice. J Immunol. 1984 Jul;133(1):227–233. [PubMed] [Google Scholar]
  10. Jones F. S., Pisetsky D. S., Kurlander R. J. Defects in mononuclear phagocytic system (MPS) function in autoimmune MRL-lpr/lpr mice. Clin Immunol Immunopathol. 1985 Jul;36(1):30–39. doi: 10.1016/0090-1229(85)90036-4. [DOI] [PubMed] [Google Scholar]
  11. Kelley V. E., Roths J. B. Increase in macrophage Ia expression in autoimmune mice: role of the Ipr gene. J Immunol. 1982 Sep;129(3):923–925. [PubMed] [Google Scholar]
  12. Kobayashi M., Plunkett J. M., Masunaka I. K., Yamamoto R. S., Granger G. A. The human LT system. XII. Purification and functional studies of LT and "TNF-like" LT forms from a continuous human T cell line. J Immunol. 1986 Sep 15;137(6):1885–1892. [PubMed] [Google Scholar]
  13. Kofler R., Schreiber R. D., Dixon F. J., Theofilopoulos A. N. Macrophage I-A/I-E expression and macrophage-stimulating lymphokines in murine lupus. Cell Immunol. 1984 Aug;87(1):92–100. doi: 10.1016/0008-8749(84)90133-3. [DOI] [PubMed] [Google Scholar]
  14. Le J., Prensky W., Henriksen D., Vilcek J. Synthesis of alpha and gamma interferons by a human cutaneous lymphoma with helper T-cell phenotype. Cell Immunol. 1982 Sep 1;72(1):157–165. doi: 10.1016/0008-8749(82)90293-3. [DOI] [PubMed] [Google Scholar]
  15. Lu C. Y., Unanue E. R. Spontaneous T-cell lymphokine production and enhanced macrophage Ia expression and tumoricidal activity in MRL-lpr mice. Clin Immunol Immunopathol. 1982 Nov;25(2):213–222. doi: 10.1016/0090-1229(82)90184-2. [DOI] [PubMed] [Google Scholar]
  16. Magilavy D. B., Hundley T. R., Steinberg A. D., Katona I. M. Hepatic reticuloendothelial system activation in autoimmune mice: differences between (NZB X NZW)F1 and MRL-lpr/lpr strains. Clin Immunol Immunopathol. 1987 Mar;42(3):386–398. doi: 10.1016/0090-1229(87)90027-4. [DOI] [PubMed] [Google Scholar]
  17. McLean I. W., Nakane P. K. Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974 Dec;22(12):1077–1083. doi: 10.1177/22.12.1077. [DOI] [PubMed] [Google Scholar]
  18. Morrison A. D., Pruzanski W., Ranadive N. S. Release of lysosomal enzymes from human polymorphonuclear leukocytes by soluble intermediate immune complexes. Scand J Rheumatol. 1978;7(4):241–246. doi: 10.3109/03009747809095663. [DOI] [PubMed] [Google Scholar]
  19. Morse H. C., 3rd, Davidson W. F., Yetter R. A., Murphy E. D., Roths J. B., Coffman R. L. Abnormalities induced by the mutant gene Ipr: expansion of a unique lymphocyte subset. J Immunol. 1982 Dec;129(6):2612–2615. [PubMed] [Google Scholar]
  20. Mountz J. D., Huppi K. E., Seldin M. F., Mushinski J. F., Steinberg A. D. T cell receptor gene expression in autoimmune mice. J Immunol. 1986 Aug 1;137(3):1029–1036. [PubMed] [Google Scholar]
  21. Nakane P. K., Kawaoi A. Peroxidase-labeled antibody. A new method of conjugation. J Histochem Cytochem. 1974 Dec;22(12):1084–1091. doi: 10.1177/22.12.1084. [DOI] [PubMed] [Google Scholar]
  22. Nakanishi A., Ashiba T., Imai Y., Osawa T. Functional defects of culture-grown bone marrow-derived macrophages from autoimmune MRL/MpJ-lpr/lpr mice. Microbiol Immunol. 1987;31(2):155–167. doi: 10.1111/j.1348-0421.1987.tb03079.x. [DOI] [PubMed] [Google Scholar]
  23. Nemazee D. A., Studer S., Steinmetz M., Dembić Z., Kiefer M. The lymphoproliferating cells of MRL-lpr/lpr mice are a polyclonal population that bear the T lymphocyte receptor for antigen. Eur J Immunol. 1985 Aug;15(8):760–764. doi: 10.1002/eji.1830150804. [DOI] [PubMed] [Google Scholar]
  24. Nose M., Nishimura M., Kyogoku M. Analysis of granulomatous arteritis in MRL/Mp autoimmune disease mice bearing lymphoproliferative genes. The use of mouse genetics to dissociate the development of arteritis and glomerulonephritis. Am J Pathol. 1989 Aug;135(2):271–280. [PMC free article] [PubMed] [Google Scholar]
  25. Nose M., Wigzell H. Biological significance of carbohydrate chains on monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6632–6636. doi: 10.1073/pnas.80.21.6632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Patarca R., Wei F. Y., Singh P., Morasso M. I., Cantor H. Dysregulated expression of the T cell cytokine Eta-1 in CD4-8- lymphocytes during the development of murine autoimmune disease. J Exp Med. 1990 Oct 1;172(4):1177–1183. doi: 10.1084/jem.172.4.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Russell P. J., Steinberg A. D. Studies of peritoneal macrophage function in mice with systemic lupus erythematosus: depressed phagocytosis of opsonized sheep erythrocytes in vitro. Clin Immunol Immunopathol. 1983 Jun;27(3):387–402. doi: 10.1016/0090-1229(83)90091-0. [DOI] [PubMed] [Google Scholar]
  29. Salahuddin S. Z., Markham P. D., Lindner S. G., Gootenberg J., Popovic M., Hemmi H., Sarin P. S., Gallo R. C. Lymphokine production by cultured human T cells transformed by human T-cell leukemia-lymphoma virus-I. Science. 1984 Feb 17;223(4637):703–707. doi: 10.1126/science.6320367. [DOI] [PubMed] [Google Scholar]
  30. Scott C. F., Jr, Tsurufuji M., Lu C. Y., Finberg R., Sy M. S. Comparison of antigen-specific T cell responses in autoimmune MRL/Mp-lpr/lpr and MRL/Mp-+/+ mice. J Immunol. 1984 Feb;132(2):633–639. [PubMed] [Google Scholar]
  31. Singh R. P., Patarca R., Schwartz J., Singh P., Cantor H. Definition of a specific interaction between the early T lymphocyte activation 1 (Eta-1) protein and murine macrophages in vitro and its effect upon macrophages in vivo. J Exp Med. 1990 Jun 1;171(6):1931–1942. doi: 10.1084/jem.171.6.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Stossel T. P., Root R. K., Vaughan M. Phagocytosis in chronic granulomatous disease and the Chediak-Higashi syndrome. N Engl J Med. 1972 Jan 20;286(3):120–123. doi: 10.1056/NEJM197201202860302. [DOI] [PubMed] [Google Scholar]
  33. Takahashi S., Nose M., Sasaki J., Yamamoto T., Kyogoku M. IgG3 production in MRL/lpr mice is responsible for development of lupus nephritis. J Immunol. 1991 Jul 15;147(2):515–519. [PubMed] [Google Scholar]
  34. Ward P. A., Duque R. E., Sulavik M. C., Johnson K. J. In vitro and in vivo stimulation of rat neutrophils and alveolar macrophages by immune complexes. Production of O-2 and H2O2. Am J Pathol. 1983 Mar;110(3):297–309. [PMC free article] [PubMed] [Google Scholar]
  35. Wofsy D., Hardy R. R., Seaman W. E. The proliferating cells in autoimmune MRL/lpr mice lack L3T4, an antigen on "helper" T cells that is involved in the response to class II major histocompatibility antigens. J Immunol. 1984 Jun;132(6):2686–2689. [PubMed] [Google Scholar]
  36. Yamashita U. Dysfunction of Ia-positive antigen-presenting cells in autoimmune mice. Cell Immunol. 1986 Feb;97(2):257–266. doi: 10.1016/0008-8749(86)90396-5. [DOI] [PubMed] [Google Scholar]
  37. Yamashita U., Shirakawa F., Nakamura H. Production of interleukin 1 by adult T cell leukemia (ATL) cell lines. J Immunol. 1987 May 15;138(10):3284–3289. [PubMed] [Google Scholar]
  38. Yui M. A., Brissette W. H., Brennan D. C., Wuthrich R. P., Rubin-Kelley V. E. Increased macrophage colony-stimulating factor in neonatal and adult autoimmune MRL-lpr mice. Am J Pathol. 1991 Aug;139(2):255–261. [PMC free article] [PubMed] [Google Scholar]

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