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. 1988 Jan 1;167(1):30–42. doi: 10.1084/jem.167.1.30

The effect of phenolic glycolipid-1 from Mycobacterium leprae on the antimicrobial activity of human macrophages

PMCID: PMC2188820  PMID: 2826638

Abstract

Purified PGL-1 and dPGL from M. leprae can prevent bacterial killing by intact phagocytes and cell-free antimicrobial systems. Both glycolipids completely abolished the antimicrobial effect of the acetaldehyde-XO- Fe2+ system. Because the cytotoxicity of this system is inhibited by catalase, SOD, mannitol, and ethanol, but not by heated SOD or catalase, these data suggest that toxicity is due to OH. generated by the Haber-Weiss reaction. That the antimicrobial killing in the XO system is completely blocked by the addition of PGL-1 or dPGL suggests that these glycolipids can act as OH. scavengers. A modest protective effect against the cytotoxicity of the MPO-H2O2-halide system by both PGL-1 and dPGL was also observed. The antimicrobial activity of the MPO system was abolished with chloride, but not iodide, as the halide. The effect of the M. leprae-derived glycolipid on bacterial killing by intact phagocytes was examined. Two linking antibodies were used to bind the dPGL to a rapidly growing test organism, S. aureus, a murine IgM mAb specific for the terminal glycoside of PGL-1, and a rabbit IgG anti-mouse IgM which bound the staphylococcal protein A via its Fc region. Examination by transmission EM of human monocyte-derived macrophages which had ingested staphylococci either coated with both antibodies and dPGL, or coated only with the IgG and IgM antibodies, demonstrated the presence of bacteria in phagosomes of control and IFN- gamma-activated macrophages. Activation of the macrophage monolayers by pretreatment with IFN-gamma markedly increased their staphylocidal activity. When dPGL coated staphylococci were ingested, killing by both control and IFN-gamma-activated macrophages was completely blocked. These results, suggesting that PGL-1 can scavenge reactive oxygen species and prevent microbial death within the phagosome, may in part explain the intracellular survival of M. leprae in certain cell types.

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Selected References

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  1. Anderson S. E., Jr, Remington J. S. Effect of normal and activated human macrophages on Toxoplasma gondii. J Exp Med. 1974 May 1;139(5):1154–1174. doi: 10.1084/jem.139.5.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bainton D. R., Golde D. W. Differentiation of macrophages from normal human bone marrow in liquid culture. Electron microscopy and cytochemistry. J Clin Invest. 1978 Jun;61(6):1555–1569. doi: 10.1172/JCI109076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhardwaj N., Nash T. W., Horwitz M. A. Interferon-gamma-activated human monocytes inhibit the intracellular multiplication of Legionella pneumophila. J Immunol. 1986 Oct 15;137(8):2662–2669. [PubMed] [Google Scholar]
  4. Brennan P. J. The phthiocerol-containing surface lipids of Mycobacterium leprae--a perspective of past and present work. Int J Lepr Other Mycobact Dis. 1983 Sep;51(3):387–396. [PubMed] [Google Scholar]
  5. Breton-Gorius J., Guichard J., Vainchenker W., Vilde J. L. Ultrastructural and cytochemical changes induced by short and prolonged culture of human monocytes. J Reticuloendothel Soc. 1980 Mar;27(3):289–301. [PubMed] [Google Scholar]
  6. Brett S. J., Draper P., Payne S. N., Rees R. J. Serological activity of a characteristic phenolic glycolipid from Mycobacterium leprae in sera from patients with leprosy and tuberculosis. Clin Exp Immunol. 1983 May;52(2):271–279. [PMC free article] [PubMed] [Google Scholar]
  7. Brett S. J., Payne S. N., Gigg J., Burgess P., Gigg R. Use of synthetic glycoconjugates containing the Mycobacterium leprae specific and immunodominant epitope of phenolic glycolipid I in the serology of leprosy. Clin Exp Immunol. 1986 Jun;64(3):476–483. [PMC free article] [PubMed] [Google Scholar]
  8. Cho S. N., Fujiwara T., Hunter S. W., Rea T. H., Gelber R. H., Brennan P. J. Use of an artificial antigen containing the 3,6-di-O-methyl-beta-D-glucopyranosyl epitope for the serodiagnosis of leprosy. J Infect Dis. 1984 Sep;150(3):311–322. doi: 10.1093/infdis/150.3.311. [DOI] [PubMed] [Google Scholar]
  9. Cho S. N., Hunter S. W., Gelber R. H., Rea T. H., Brennan P. J. Quantitation of the phenolic glycolipid of Mycobacterium leprae and relevance to glycolipid antigenemia in leprosy. J Infect Dis. 1986 Mar;153(3):560–569. doi: 10.1093/infdis/153.3.560. [DOI] [PubMed] [Google Scholar]
  10. Drutz D. J., Chen T. S., Lu W. H. The continuous bacteremia of lepromatous leprosy. N Engl J Med. 1972 Jul 27;287(4):159–164. doi: 10.1056/NEJM197207272870402. [DOI] [PubMed] [Google Scholar]
  11. Drutz D. J., O'Neill S. M., Levy L. Viability of blood-borne Mycobacterium leprae. J Infect Dis. 1974 Sep;130(3):288–292. doi: 10.1093/infdis/130.3.288. [DOI] [PubMed] [Google Scholar]
  12. Holzer T. J., Nelson K. E., Crispen R. G., Andersen B. R. Mycobacterium leprae fails to stimulate phagocytic cell superoxide anion generation. Infect Immun. 1986 Feb;51(2):514–520. doi: 10.1128/iai.51.2.514-520.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hunter S. W., Brennan P. J. A novel phenolic glycolipid from Mycobacterium leprae possibly involved in immunogenicity and pathogenicity. J Bacteriol. 1981 Sep;147(3):728–735. doi: 10.1128/jb.147.3.728-735.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hunter S. W., Fujiwara T., Brennan P. J. Structure and antigenicity of the major specific glycolipid antigen of Mycobacterium leprae. J Biol Chem. 1982 Dec 25;257(24):15072–15078. [PubMed] [Google Scholar]
  15. Kaplan G., Van Voorhis W. C., Sarno E. N., Nogueira N., Cohn Z. A. The cutaneous infiltrates of leprosy. A transmission electron microscopy study. J Exp Med. 1983 Oct 1;158(4):1145–1159. doi: 10.1084/jem.158.4.1145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klebanoff S. J., Shepard C. C. Toxic effect of the peroxidase-hydrogen peroxide-halide antimicrobial system on Mycobacterium leprae. Infect Immun. 1984 May;44(2):534–536. doi: 10.1128/iai.44.2.534-536.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klebanoff S. J., Waltersdorph A. M., Rosen H. Antimicrobial activity of myeloperoxidase. Methods Enzymol. 1984;105:399–403. doi: 10.1016/s0076-6879(84)05055-2. [DOI] [PubMed] [Google Scholar]
  18. Lygren S. T., Closs O., Bercouvier H., Wayne L. G. Catalases, peroxidases, and superoxide dismutases in Mycobacterium leprae and other mycobacteria studied by crossed immunoelectrophoresis and polyacrylamide gel electrophoresis. Infect Immun. 1986 Dec;54(3):666–672. doi: 10.1128/iai.54.3.666-672.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Murray H. W., Rubin B. Y., Rothermel C. D. Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine. J Clin Invest. 1983 Oct;72(4):1506–1510. doi: 10.1172/JCI111107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nakagawara A., Nathan C. F., Cohn Z. A. Hydrogen peroxide metabolism in human monocytes during differentiation in vitro. J Clin Invest. 1981 Nov;68(5):1243–1252. doi: 10.1172/JCI110370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Neill M. A., Henderson W. R., Klebanoff S. J. Oxidative degradation of leukotriene C4 by human monocytes and monocyte-derived macrophages. J Exp Med. 1985 Nov 1;162(5):1634–1644. doi: 10.1084/jem.162.5.1634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Neill M. A., Hightower A. W., Broome C. V. Leprosy in the United States, 1971-1981. J Infect Dis. 1985 Nov;152(5):1064–1069. doi: 10.1093/infdis/152.5.1064. [DOI] [PubMed] [Google Scholar]
  24. Rosen H., Klebanoff S. J. Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte. J Exp Med. 1979 Jan 1;149(1):27–39. doi: 10.1084/jem.149.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rosen H., Klebanoff S. J. Role of iron and ethylenediaminetetraacetic acid in the bactericidal activity of a superoxide anion-generating system. Arch Biochem Biophys. 1981 May;208(2):512–519. doi: 10.1016/0003-9861(81)90539-7. [DOI] [PubMed] [Google Scholar]
  26. Rothermel C. D., Rubin B. Y., Murray H. W. Gamma-interferon is the factor in lymphokine that activates human macrophages to inhibit intracellular Chlamydia psittaci replication. J Immunol. 1983 Nov;131(5):2542–2544. [PubMed] [Google Scholar]
  27. Sansonetti P., Lagrange P. H. The immunology of leprosy: speculations on the leprosy spectrum. Rev Infect Dis. 1981 May-Jun;3(3):422–469. doi: 10.1093/clinids/3.3.422. [DOI] [PubMed] [Google Scholar]
  28. Sharp A. K., Colston M. J., Banerjee D. K. Susceptibility of Mycobacterium leprae to the bactericidal activity of mouse peritoneal macrophages and to hydrogen peroxide. J Med Microbiol. 1985 Feb;19(1):77–84. doi: 10.1099/00222615-19-1-77. [DOI] [PubMed] [Google Scholar]
  29. Wheeler P. R., Gregory D. Superoxide dismutase, peroxidatic activity and catalase in Mycobacterium leprae purified from armadillo liver. J Gen Microbiol. 1980 Dec;121(2):457–464. doi: 10.1099/00221287-121-2-457. [DOI] [PubMed] [Google Scholar]
  30. Young D. B., Buchanan T. M. A serological test for leprosy with a glycolipid specific for Mycobacterium leprae. Science. 1983 Sep 9;221(4615):1057–1059. doi: 10.1126/science.6348948. [DOI] [PubMed] [Google Scholar]
  31. Young D. B., Dissanayake S., Miller R. A., Khanolkar S. R., Buchanan T. M. Humans respond predominantly with IgM immunoglobulin to the species-specific glycolipid of Mycobacterium leprae. J Infect Dis. 1984 Jun;149(6):870–873. doi: 10.1093/infdis/149.6.870. [DOI] [PubMed] [Google Scholar]
  32. Young D. B., Harnisch J. P., Knight J., Buchanan T. M. Detection of phenolic glycolipid I in sera from patients with lepromatous leprosy. J Infect Dis. 1985 Nov;152(5):1078–1081. doi: 10.1093/infdis/152.5.1078. [DOI] [PubMed] [Google Scholar]
  33. Young D. B., Khanolkar S. R., Barg L. L., Buchanan T. M. Generation and characterization of monoclonal antibodies to the phenolic glycolipid of Mycobacterium leprae. Infect Immun. 1984 Jan;43(1):183–188. doi: 10.1128/iai.43.1.183-188.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. van den Broek P. J., Buys L. F., van Furth R. Adherence of lysostaphin to and penetration into human monocytes. Scand J Immunol. 1985 Feb;21(2):189–193. doi: 10.1111/j.1365-3083.1985.tb01419.x. [DOI] [PubMed] [Google Scholar]

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