Home LiteratureArticle Details
PMID: 7931080 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guérin.

The Journal of experimental medicine ·Vol. 180 ·No. 4 ·1994-10-01 ·Pages 1499-509

Molloy A, Laochumroonvorapong P, Kaplan G

Abstract

We have examined the effect of killing of host monocytes infected with bacillus Calmette-Guérin (BCG) on the viability of the intracellular mycobacteria. Peripheral blood monocytes were infected in vitro with a single bacillus per cell and maintained in culture for 6-8 d to allow the bacilli to replicate. Replicating viable BCG were found singly in perinuclear vacuoles bounded by tightly apposed lipid bilayers. Monocytes were then exposed to toxic mediators that induced killing of cells as evaluated by 51Cr release into the culture medium. Both hydrogen peroxide (H2O2) (an inducer of cell necrosis) and adenosine triphosphate (ATP4-) (an inducer of cell apoptosis) treatment killed infected monocytes. H2O2-induced killing had no effect on BCG viability. ATP-induced cell death was accompanied by DNA fragmentation and nuclear condensation. Apoptosis was associated with a swelling of the phagocytic vacuoles which became multibacillary and with a reduction of BCG viability as enumerated by colony-forming units.

MeSH Terms
Adenosine Triphosphate/pharmacology Apoptosis Blood Bactericidal Activity CD4-Positive T-Lymphocytes/immunology Cells, Cultured DNA/metabolism Guanosine Triphosphate/pharmacology Humans Hydrogen Peroxide/pharmacology Monocytes/immunology,microbiology,pathology Mycobacterium bovis/immunology,ultrastructure Necrosis Vacuoles/ultrastructure
Chemicals
Guanosine Triphosphate Adenosine Triphosphate DNA Hydrogen Peroxide
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Molloy A
Department of Cellular Physiology and Immunology, Rockefeller University, New York 10021.
Laochumroonvorapong P
Kaplan G
References (42)
42 references, click to expand
  1. Recognition and destruction of Bacillus Calmette-Guerin-infected human monocytes.
    J Exp Med. 1993 Jun 1;177(6):1691-8 PMID: 7684432
  2. Sequestration from immune CD4+ T cells of mycobacteria growing in human macrophages.
    Science. 1993 May 14;260(5110):984-6 PMID: 8098550
  3. Gamma interferon activates human macrophages to become tumoricidal and leishmanicidal but enhances replication of macrophage-associated mycobacteria.
    Infect Immun. 1985 Oct;50(1):1-8 PMID: 3930401
  4. Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis.
    J Immunol. 1988 Oct 15;141(8):2629-34 PMID: 3171180
  5. Multiplication and survival of tubercle bacilli in the organs of mice.
    J Exp Med. 1953 Feb 1;97(2):189-206 PMID: 13022873
  6. IFN-gamma-producing ability as a possible marker for the protective T cells against Mycobacterium bovis BCG in mice.
    J Immunol. 1992 May 1;148(9):2887-93 PMID: 1374103
  7. Cell death in granulomata: the role of apoptosis.
    J Clin Pathol. 1987 Nov;40(11):1314-9 PMID: 3320094
  8. Killing of target cells by lymphocytes: a mechanistic view.
    Physiol Rev. 1989 Jan;69(1):250-314 PMID: 2643124
  9. EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS : THE ROUTE OF INFECTION IN NATURALLY ACQUIRED TUBERCULOSIS OF THE GUINEA PIG.
    J Exp Med. 1930 Apr 30;51(5):769-76 PMID: 19869726
  10. The emergence of drug-resistant tuberculosis in New York City.
    N Engl J Med. 1993 Feb 25;328(8):521-6 PMID: 8381207
  11. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase.
    Science. 1994 Feb 4;263(5147):678-81 PMID: 8303277
  12. Gliotoxin induces apoptosis in macrophages unrelated to its antiphagocytic properties.
    J Biol Chem. 1988 Dec 5;263(34):18493-9 PMID: 2461370
  13. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes.
    Immunology. 1986 Jan;57(1):159-63 PMID: 3002968
  14. Apoptosis reduces both the in vitro replication and the in vivo infectivity of a baculovirus.
    J Virol. 1993 Jul;67(7):3730-8 PMID: 8510202
  15. Phagosome-lysosome interactions in cultured macrophages infected with virulent tubercle bacilli. Reversal of the usual nonfusion pattern and observations on bacterial survival.
    J Exp Med. 1975 Jul 1;142(1):1-16 PMID: 807671
  16. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation.
    Nature. 1980 Apr 10;284(5756):555-6 PMID: 6245367
  17. Immunopathology of BCG infection in genetically resistant and susceptible mouse strains.
    J Immunol. 1982 Nov;129(5):2179-85 PMID: 6749986
  18. Disruption of phagosomal membranes of normal alveolar macrophages by the H37Rv strain of Mycobacterium tuberculosis. A correlate of virulence.
    Am Rev Respir Dis. 1984 Feb;129(2):322-8 PMID: 6421212
  19. Gamma interferon limits access of Listeria monocytogenes to the macrophage cytoplasm.
    J Exp Med. 1989 Dec 1;170(6):2141-6 PMID: 2511268
  20. Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli.
    Cell Prolif. 1991 Mar;24(2):203-14 PMID: 2009322
  21. Host-parasite relationships in experimental airborne tuberculosis. 3. Relevance of microbial enumeration to acquired resistance in guinea pigs.
    Am Rev Respir Dis. 1970 Sep;102(3):422-9 PMID: 5450906
  22. Apoptosis.
    Immunol Today. 1993 Mar;14(3):126-30 PMID: 8466628
  23. Responses of mouse lymphocytes to extracellular ATP. II. Extracellular ATP causes cell type-dependent lysis and DNA fragmentation.
    J Immunol. 1990 Sep 1;145(5):1545-50 PMID: 2384670
  24. Toward an understanding of the molecular mechanisms of physiological cell death.
    Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):786-9 PMID: 8430086
  25. Mycobacterial virulence. Virulent strains of Mycobacteria tuberculosis have faster in vivo doubling times and are better equipped to resist growth-inhibiting functions of macrophages in the presence and absence of specific immunity.
    J Exp Med. 1993 Jun 1;177(6):1723-33 PMID: 8496688
  26. Immunity to intracellular bacteria.
    Annu Rev Immunol. 1993;11:129-63 PMID: 8476559
  27. Apoptosis and programmed cell death in immunity.
    Annu Rev Immunol. 1992;10:267-93 PMID: 1590988
  28. Apoptosis: final control point in cell biology.
    Trends Cell Biol. 1992 Sep;2(9):263-7 PMID: 14731518
  29. Characteristics and specificity of acquired immunologic memory to Mycobacterium tuberculosis infection.
    J Immunol. 1988 May 15;140(10):3589-93 PMID: 3129497
  30. Mycobacteria-reactive Lyt-2+ T cell lines.
    Eur J Immunol. 1988 Jan;18(1):59-66 PMID: 2450033
  31. The immunology of antituberculous immunity.
    Am Rev Respir Dis. 1968 Mar;97(3):337-44 PMID: 4966267
  32. Tuberculosis as a manifestation of the acquired immunodeficiency syndrome (AIDS).
    JAMA. 1986 Jul 18;256(3):362-6 PMID: 3723722
  33. Activation of macrophages to inhibit proliferation of Mycobacterium tuberculosis: comparison of the effects of recombinant gamma-interferon on human monocytes and murine peritoneal macrophages.
    Immunology. 1986 Nov;59(3):333-8 PMID: 3098676
  34. Shigella flexneri induces apoptosis in infected macrophages.
    Nature. 1992 Jul 9;358(6382):167-9 PMID: 1614548
  35. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes.
    J Exp Med. 1971 Sep 1;134(3 Pt 1):713-40 PMID: 15776571
  36. Regulation of apoptosis by the transforming genes of the DNA tumor virus adenovirus.
    Proc Soc Exp Biol Med. 1993 Oct;204(1):30-9 PMID: 7690485
  37. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection.
    Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12013-7 PMID: 1465432
  38. Extracellular ATP as a trigger for apoptosis or programmed cell death.
    J Cell Biol. 1991 Jan;112(2):279-88 PMID: 1988462
  39. Programmed cell death of T lymphocytes during acute viral infection: a mechanism for virus-induced immune deficiency.
    J Virol. 1993 Oct;67(10):5754-65 PMID: 8371341
  40. Tuberculosis: commentary on a reemergent killer.
    Science. 1992 Aug 21;257(5073):1055-64 PMID: 1509256
  41. IFN-gamma enhances sensitivity of human macrophages to extracellular ATP-mediated lysis.
    J Immunol. 1991 Oct 15;147(8):2579-85 PMID: 1918978
  42. Pathogenesis of tuberculosis: interaction of Mycobacterium tuberculosis with macrophages.
    Infect Immun. 1993 Jul;61(7):2763-73 PMID: 8514378
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.180.4.1499
Published
1994-10-01
Pages
1499-509
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191680
Subset
IM
Grants
NIAID NIH HHS · AI-07012 · United States
NIAID NIH HHS · AI-22616 · United States
External Links
PubMed source DOI: 10.1084/jem.180.4.1499 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2