A synergistic interaction between Bacillus Calmette-Guérin (BCG) and NADPH oxidase stimulants on the production of reactive oxygen metabolites by human mononuclear phagocytes

Our plain-English summary of A synergistic interaction between Bacillus Calmette-Guérin (BCG) and NADPH oxidase stimulants on the production of reactive oxygen metabolites by human mononuclear phagocytes, by P.W. Nyberg, S.A. Nordman, L. Linko (APMIS, 1994).

The study

• Authors: P.W. Nyberg, S.A. Nordman, L. Linko
• Journal: APMIS
• Published: 1994;102(1):67-71
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Bacillus Calmette-Guérin (BCG) was added simultaneously with known NADPH oxidase stimulants to suspensions of human mononuclear leukocytes, and the subsequent production of reactive oxygen metabolites (ROMs) was studied by luminol-dependent chemiluminescence. BCG significantly amplified the ROM responses induced by zymosan, phorbol myristate acetate (PMA), and quartz, but not by concanavalin A and asbestos fibers. The stimulatory effect occurred rapidly when BCG was added to cells already phagocytosing zymosan, and vanished rapidly when extracellular BCG was removed from adherent monocyte cultures by washing prior to the addition of zymosan. The stimulatory effect of BCG could not be reproduced with recombinant interferon-gamma, tuberculin PPD, muramyl dipeptide, nor with the apathogenic Mycobacterium tuberculosis strain RV37. BCG and zymosan or PMA that had been incubated together prior to addition to the mononuclear cell suspensions caused ROM production with faster kinetics than if the reagents were added separately without preincubation. In conclusion, the synergy between BCG and some of the NADPH oxidase stimulants seems to be due to an interaction between BCG and the NADPH oxidase stimulants rather than to an interaction between BCG and the ROM-producing cells. Such interactions between mycobacteria and NADPH oxidase stimulants may be of importance as a factor affecting the individual susceptibility to tissue damage in tuberculosis, for example in silicotuberculosis.

In plain English

This was a laboratory study from Finland. The authors took mononuclear white blood cells, a group that includes monocytes, from healthy volunteers. Using a light-emission test, they measured how much reactive oxygen the cells produced. The cells were exposed to five known stimulants, including quartz and standard chrysotile asbestos, with and without BCG, the bacterium used in the tuberculosis vaccine. All five stimulants made the cells produce reactive oxygen, while BCG alone caused only negligible production. Adding BCG caused a statistically significant increase in the response to zymosan, PMA and quartz, but not to concanavalin A or chrysotile asbestos. The strongest combined effects were with zymosan or PMA. A harmless tuberculosis strain (RV37), tuberculin PPD and muramyl dipeptide did not reproduce the BCG effect. The effect disappeared when free BCG was washed away before zymosan was added. The authors concluded that BCG seemed to interact mainly with the stimulating agents rather than with the cells. They stated that the biochemical nature of this interaction remained unclear. The study used cells in the laboratory, not people exposed to asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on human blood cells, measuring reactive oxygen production by luminol-dependent chemiluminescence
• Who was studied: Mononuclear white blood cells (including monocytes) taken from the blood of healthy volunteers. The main comparison was repeated in five separate experiments, each using cells from a different person. The work was done at Mjolbolsta Hospital, Finland.
• Exposure: Cells were exposed to standard chrysotile asbestos, quartz, zymosan, phorbol myristate acetate (PMA) and concanavalin A, each with and without BCG (Bacillus Calmette-Guérin). Chrysotile and quartz were used at the same concentration, printed in the scan as '50 pg/ml'.
• Main results:
  • All five stimulants, including chrysotile asbestos and quartz, caused the cells to produce reactive oxygen.
  • BCG alone caused only negligible reactive oxygen production.
  • Adding BCG significantly increased the reactive oxygen response to zymosan, PMA and quartz, but not the response to concanavalin A or chrysotile asbestos (five experiments, Wilcoxon's test).
  • The strongest combined effects were seen when BCG was combined with zymosan or PMA.
  • Tuberculin PPD and muramyl dipeptide, both components of mycobacteria, had no stimulatory effect, and the apathogenic Mycobacterium tuberculosis RV37 strain caused no stimulation.
  • Pre-treating attached monocytes with BCG for 1 hour did not increase the zymosan response once the remaining free BCG had been washed off.
  • When BCG was incubated together with zymosan or PMA before being added to the cells, the response peaked earlier and higher than when the agents were added separately.
• The authors' conclusion: The authors concluded that their observations suggested BCG interacted mainly with the agents that triggered reactive oxygen production, not with the cells that produced it.
• Limitations the authors state:
  • The authors stated that the biochemical nature of the interaction between BCG and the stimulants remained unclear.

Related studies

• Production of reactive oxygen species by phagocytic cells after exposure to glass wool and stone wool fibres - effect of fibre preincubation in aqueous solution — T. Zoller, W.J. Zeller (2000)
• Polyvinylpyridine-N-oxide and carboxymethyl cellulose inhibit mineral dust-induced production of reactive oxygen species by human macrophages — P. Nyberg (1991)
• Inhibition of NADPH oxidase 4 induces apoptosis in malignant mesothelioma: Role of reactive oxygen species — M. Tanaka, Y. Miura, et al. (2015)
• Changes in free intracellular calcium and production of reactive oxygen metabolites in human leukocytes by soluble and particulate stimuli — M. Tuomala, M.R. Hirvonen, et al. (1993)
• Production of reactive oxygen metabolites induced by asbestos fibres in human polymorphonuclear leucocytes — M. Hedenborg, M. Klockars (1987)
• Chemiluminescent detection of induced reactive oxygen metabolite production of human polymorphonuclear leucocytes by anthophyllite asbestos — T. Iwata, N. Kohyama, et al. (2002)

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