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. 1997 May;65(5):1931–1935. doi: 10.1128/iai.65.5.1931-1935.1997

Production of tumor necrosis factor and nitric oxide by macrophages infected with live and dead mycobacteria and their suppression by an interleukin-10-secreting recombinant.

B G Marshall 1, M A Chambers 1, A Wangoo 1, R J Shaw 1, D B Young 1
PMCID: PMC175244  PMID: 9125582

Abstract

We have analyzed mycobacterium-induced cytokine secretion in the J774A.1 macrophage-like cell line. Tumor necrosis factor alpha (TNF-alpha) was preferentially induced by live organisms, both slow and rapid growing. Expression of interleukin-10 by a recombinant strain of Mycobacterium smegmatis caused reduced production of TNF-alpha and nitric oxide during the early stages of infection.

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Selected References

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  1. Barnes P. F., Chatterjee D., Abrams J. S., Lu S., Wang E., Yamamura M., Brennan P. J., Modlin R. L. Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. J Immunol. 1992 Jul 15;149(2):541–547. [PubMed] [Google Scholar]
  2. Behling C. A., Perez R. L., Kidd M. R., Staton G. W., Jr, Hunter R. L. Induction of pulmonary granulomas, macrophage procoagulant activity, and tumor necrosis factor-alpha by trehalose glycolipids. Ann Clin Lab Sci. 1993 Jul-Aug;23(4):256–266. [PubMed] [Google Scholar]
  3. Chambers M. A., Marshall B. G., Wangoo A., Bune A., Cook H. T., Shaw R. J., Young D. B. Differential responses to challenge with live and dead Mycobacterium bovis Bacillus Calmette-Guérin. J Immunol. 1997 Feb 15;158(4):1742–1748. [PubMed] [Google Scholar]
  4. Chan J., Xing Y., Magliozzo R. S., Bloom B. R. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J Exp Med. 1992 Apr 1;175(4):1111–1122. doi: 10.1084/jem.175.4.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chao C. W. Post vaccination keloid. Bull Int Union Tuberc. 1972 Aug;47 (Suppl 2):178–178. [PubMed] [Google Scholar]
  6. Chatterjee D., Roberts A. D., Lowell K., Brennan P. J., Orme I. M. Structural basis of capacity of lipoarabinomannan to induce secretion of tumor necrosis factor. Infect Immun. 1992 Mar;60(3):1249–1253. doi: 10.1128/iai.60.3.1249-1253.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Corradin S. B., Fasel N., Buchmüller-Rouiller Y., Ransijn A., Smith J., Mauël J. Induction of macrophage nitric oxide production by interferon-gamma and tumor necrosis factor-alpha is enhanced by interleukin-10. Eur J Immunol. 1993 Aug;23(8):2045–2048. doi: 10.1002/eji.1830230851. [DOI] [PubMed] [Google Scholar]
  8. Dahl K. E., Shiratsuchi H., Hamilton B. D., Ellner J. J., Toossi Z. Selective induction of transforming growth factor beta in human monocytes by lipoarabinomannan of Mycobacterium tuberculosis. Infect Immun. 1996 Feb;64(2):399–405. doi: 10.1128/iai.64.2.399-405.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Denis M. Interferon-gamma-treated murine macrophages inhibit growth of tubercle bacilli via the generation of reactive nitrogen intermediates. Cell Immunol. 1991 Jan;132(1):150–157. doi: 10.1016/0008-8749(91)90014-3. [DOI] [PubMed] [Google Scholar]
  10. Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
  11. Falcone V., Bassey E. B., Toniolo A., Conaldi P. G., Collins F. M. Differential release of tumor necrosis factor-alpha from murine peritoneal macrophages stimulated with virulent and avirulent species of mycobacteria. FEMS Immunol Med Microbiol. 1994 Mar;8(3):225–232. doi: 10.1111/j.1574-695X.1994.tb00447.x. [DOI] [PubMed] [Google Scholar]
  12. Fang J. W., Ko B. M., Wilson J. A. BCG vaccination scars: incidence and acceptance amongst British high-school children. Child Care Health Dev. 1993 Jan-Feb;19(1):37–43. doi: 10.1111/j.1365-2214.1993.tb00711.x. [DOI] [PubMed] [Google Scholar]
  13. Filley E. A., Rook G. A. Effect of mycobacteria on sensitivity to the cytotoxic effects of tumor necrosis factor. Infect Immun. 1991 Aug;59(8):2567–2572. doi: 10.1128/iai.59.8.2567-2572.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fine P. E., Ponnighaus J. M., Maine N. The distribution and implications of BCG scars in northern Malawi. Bull World Health Organ. 1989;67(1):35–42. [PMC free article] [PubMed] [Google Scholar]
  15. Flesch I. E., Kaufmann S. H. Mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages: role of reactive nitrogen intermediates. Infect Immun. 1991 Sep;59(9):3213–3218. doi: 10.1128/iai.59.9.3213-3218.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Flick D. A., Gifford G. E. Comparison of in vitro cell cytotoxic assays for tumor necrosis factor. J Immunol Methods. 1984 Mar 30;68(1-2):167–175. doi: 10.1016/0022-1759(84)90147-9. [DOI] [PubMed] [Google Scholar]
  17. Friedland J. S., Shattock R., Remick D. G., Griffin G. E. Mycobacterial 65-kD heat shock protein induces release of proinflammatory cytokines from human monocytic cells. Clin Exp Immunol. 1993 Jan;91(1):58–62. doi: 10.1111/j.1365-2249.1993.tb03354.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gazzinelli R. T., Eltoum I., Wynn T. A., Sher A. Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol. 1993 Oct 1;151(7):3672–3681. [PubMed] [Google Scholar]
  19. Gentry L. E., Nash B. W. The pro domain of pre-pro-transforming growth factor beta 1 when independently expressed is a functional binding protein for the mature growth factor. Biochemistry. 1990 Jul 24;29(29):6851–6857. doi: 10.1021/bi00481a014. [DOI] [PubMed] [Google Scholar]
  20. Hale K. K., Smith C. G., Baker S. L., Vanderslice R. W., Squires C. H., Gleason T. M., Tucker K. K., Kohno T., Russell D. A. Multifunctional regulation of the biological effects of TNF-alpha by the soluble type I and type II TNF receptors. Cytokine. 1995 Jan;7(1):26–38. doi: 10.1006/cyto.1995.1004. [DOI] [PubMed] [Google Scholar]
  21. Hart P. D., Young M. R., Gordon A. H., Sullivan K. H. Inhibition of phagosome-lysosome fusion in macrophages by certain mycobacteria can be explained by inhibition of lysosomal movements observed after phagocytosis. J Exp Med. 1987 Oct 1;166(4):933–946. doi: 10.1084/jem.166.4.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kaplan G. Cytokine regulation of disease progression in leprosy and tuberculosis. Immunobiology. 1994 Oct;191(4-5):564–568. doi: 10.1016/S0171-2985(11)80463-8. [DOI] [PubMed] [Google Scholar]
  23. Khanolkar-Young S., Rayment N., Brickell P. M., Katz D. R., Vinayakumar S., Colston M. J., Lockwood D. N. Tumour necrosis factor-alpha (TNF-alpha) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions. Clin Exp Immunol. 1995 Feb;99(2):196–202. doi: 10.1111/j.1365-2249.1995.tb05532.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Khoo K. H., Dell A., Morris H. R., Brennan P. J., Chatterjee D. Inositol phosphate capping of the nonreducing termini of lipoarabinomannan from rapidly growing strains of Mycobacterium. J Biol Chem. 1995 May 26;270(21):12380–12389. doi: 10.1074/jbc.270.21.12380. [DOI] [PubMed] [Google Scholar]
  25. Klausner J. D., Makonkawkeyoon S., Akarasewi P., Nakata K., Kasinrerk W., Corral L., Dewar R. L., Lane H. C., Freedman V. H., Kaplan G. The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Mar 1;11(3):247–257. doi: 10.1097/00042560-199603010-00005. [DOI] [PubMed] [Google Scholar]
  26. Lotte A., Wasz-Höckert O., Poisson N., Dumitrescu N., Verron M., Couvet E. BCG complications. Estimates of the risks among vaccinated subjects and statistical analysis of their main characteristics. Adv Tuberc Res. 1984;21:107–193. [PubMed] [Google Scholar]
  27. Murray P. J., Aldovini A., Young R. A. Manipulation and potentiation of antimycobacterial immunity using recombinant bacille Calmette-Guérin strains that secrete cytokines. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):934–939. doi: 10.1073/pnas.93.2.934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nussler A. K., Billiar T. R. Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol. 1993 Aug;54(2):171–178. [PubMed] [Google Scholar]
  29. O'Donnell M. A., Aldovini A., Duda R. B., Yang H., Szilvasi A., Young R. A., DeWolf W. C. Recombinant Mycobacterium bovis BCG secreting functional interleukin-2 enhances gamma interferon production by splenocytes. Infect Immun. 1994 Jun;62(6):2508–2514. doi: 10.1128/iai.62.6.2508-2514.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Orges González I. Prevalencia de cicatrices hipertróficas y queloides según el sitio de aplicación de la vacuna BCG intradérmica. Bol Oficina Sanit Panam. 1980 Jun;88(6):481–488. [PubMed] [Google Scholar]
  31. Oswald I. P., Gazzinelli R. T., Sher A., James S. L. IL-10 synergizes with IL-4 and transforming growth factor-beta to inhibit macrophage cytotoxic activity. J Immunol. 1992 Jun 1;148(11):3578–3582. [PubMed] [Google Scholar]
  32. Piguet P. F., Tacchini-Cottier F., Vesin C. Administration of anti-TNF-alpha or anti-CD11a antibodies to normal adult mice decreases lung and bone collagen content: evidence for an effect on platelet consumption. Am J Respir Cell Mol Biol. 1995 Feb;12(2):227–231. doi: 10.1165/ajrcmb.12.2.7532421. [DOI] [PubMed] [Google Scholar]
  33. Ralph P., Nakoinz I. Phagocytosis and cytolysis by a macrophage tumour and its cloned cell line. Nature. 1975 Oct 2;257(5525):393–394. doi: 10.1038/257393a0. [DOI] [PubMed] [Google Scholar]
  34. Roach T. I., Barton C. H., Chatterjee D., Blackwell J. M. Macrophage activation: lipoarabinomannan from avirulent and virulent strains of Mycobacterium tuberculosis differentially induces the early genes c-fos, KC, JE, and tumor necrosis factor-alpha. J Immunol. 1993 Mar 1;150(5):1886–1896. [PubMed] [Google Scholar]
  35. Roche P. W., Triccas J. A., Winter N. BCG vaccination against tuberculosis: past disappointments and future hopes. Trends Microbiol. 1995 Oct;3(10):397–401. doi: 10.1016/s0966-842x(00)88986-6. [DOI] [PubMed] [Google Scholar]
  36. Rook G. A. Mycobacteria, cytokines and antibiotics. Pathol Biol (Paris) 1990 Apr;38(4):276–280. [PubMed] [Google Scholar]
  37. Rook G. A., al Attiyah R., Filley E. New insights into the immunopathology of tuberculosis. Pathobiology. 1991;59(3):148–152. doi: 10.1159/000163633. [DOI] [PubMed] [Google Scholar]
  38. Sanders R., Dickson M. G. BCG vaccination scars: an avoidable problem? Br Med J (Clin Res Ed) 1982 Dec 11;285(6356):1679–1680. doi: 10.1136/bmj.285.6356.1679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sarmento A. M., Appelberg R. Relationship between virulence of Mycobacterium avium strains and induction of tumor necrosis factor alpha production in infected mice and in in vitro-cultured mouse macrophages. Infect Immun. 1995 Oct;63(10):3759–3764. doi: 10.1128/iai.63.10.3759-3764.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Shiratsuchi H., Hamilton B., Toossi Z., Ellner J. J. Evidence against a role for interleukin-10 in the regulation of growth of Mycobacterium avium in human monocytes. J Infect Dis. 1996 Feb;173(2):410–417. doi: 10.1093/infdis/173.2.410. [DOI] [PubMed] [Google Scholar]
  41. Sterne J. A., Fine P. E., Pönnighaus J. M., Sibanda F., Munthali M., Glynn J. R. Does bacille Calmette-Guérin scar size have implications for protection against tuberculosis or leprosy? Tuber Lung Dis. 1996 Apr;77(2):117–123. doi: 10.1016/s0962-8479(96)90025-8. [DOI] [PubMed] [Google Scholar]
  42. Stuehr D. J., Marletta M. A. Synthesis of nitrite and nitrate in murine macrophage cell lines. Cancer Res. 1987 Nov 1;47(21):5590–5594. [PubMed] [Google Scholar]
  43. Sueoka E., Nishiwaki S., Okabe S., Iida N., Suganuma M., Yano I., Aoki K., Fujiki H. Activation of protein kinase C by mycobacterial cord factor, trehalose 6-monomycolate, resulting in tumor necrosis factor-alpha release in mouse lung tissues. Jpn J Cancer Res. 1995 Aug;86(8):749–755. doi: 10.1111/j.1349-7006.1995.tb02464.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tramontana J. M., Utaipat U., Molloy A., Akarasewi P., Burroughs M., Makonkawkeyoon S., Johnson B., Klausner J. D., Rom W., Kaplan G. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. Mol Med. 1995 May;1(4):384–397. [PMC free article] [PubMed] [Google Scholar]
  45. Vieira P., de Waal-Malefyt R., Dang M. N., Johnson K. E., Kastelein R., Fiorentino D. F., deVries J. E., Roncarolo M. G., Mosmann T. R., Moore K. W. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1172–1176. doi: 10.1073/pnas.88.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yang J., Kawamura I., Zhu H., Mitsuyama M. Involvement of natural killer cells in nitric oxide production by spleen cells after stimulation with Mycobacterium bovis BCG. Study of the mechanism of the different abilities of viable and killed BCG. J Immunol. 1995 Dec 15;155(12):5728–5735. [PubMed] [Google Scholar]
  47. Zhang Y., Lathigra R., Garbe T., Catty D., Young D. Genetic analysis of superoxide dismutase, the 23 kilodalton antigen of Mycobacterium tuberculosis. Mol Microbiol. 1991 Feb;5(2):381–391. doi: 10.1111/j.1365-2958.1991.tb02120.x. [DOI] [PubMed] [Google Scholar]

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