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Antimycobacterial effect of lysates prepared from immunologically activated macrophages
Abstract:
Lysates or heptane extracts of peritoneal (P) and alveolar (A) normal macrophages (N-M), immune macrophages (I-M), and immune-activated macrophages (IA-M) were examined for antimycobacterial activity by the agar-plate diffusion test. This test has been found suitable to reveal the antibacterial activity in 3-day incubated, but not in freshly prepared, lysates. Results showed that materials of IA-AM or I-AM and of IA-PM exerted antimycobacterial effects, whereas materials of N-PM, I-PM, and of N-AM were usually inactive. Antimycobacterial activity of lysates of AM was stronger than that of PM. The formation of antibacterial factors during an incubation of M lysates, the solubility of the factors in heptane, and various other characteristics suggested that the antimycobacterial effect was caused by the formation of toxic levels of non-esterified fatty acids. M lysates exerted equal activities against BCG, H(37)Ra, and H(37)Rv strains of tubercle bacilli. The presence of antimycobacterial activity in lysates prepared from IA-M of either BCG- or BCG-sensitized animals indicated that the potential to generate antimycobacterial activity is associated with the state of delayed hypersensitivity and the state of activation of M.
Insights
Activated macrophages produce antimycobacterial factors, primarily non-esterified fatty acids, effective against various tuberculosis strains. This activity is linked to delayed hypersensitivity and macrophage activation states.
Area of Science:
- Immunology
- Microbiology
Background:
- Macrophages play a crucial role in the immune response against microbial infections.
- Understanding the mechanisms by which macrophages combat Mycobacterium tuberculosis is essential for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the antimycobacterial activity of normal, immune, and immune-activated macrophages (M).
- To identify the nature of the antimycobacterial factors produced by macrophages.
Main Methods:
- Lysates and heptane extracts of peritoneal (P) and alveolar (A) macrophages were prepared.
- Antimycobacterial activity was assessed using the agar-plate diffusion test against Mycobacterium tuberculosis strains (BCG, H37Ra, H37Rv).
- Incubation of lysates was performed to assess factor formation and stability.
Main Results:
- Immune-activated alveolar and peritoneal macrophages (IA-AM, IA-PM) and immune alveolar macrophages (I-AM) exhibited significant antimycobacterial effects.
- Normal peritoneal macrophages (N-PM), immune peritoneal macrophages (I-PM), and normal alveolar macrophages (N-AM) generally showed inactive results.
- Alveolar macrophage lysates demonstrated stronger antimycobacterial activity than peritoneal macrophage lysates.
- The activity was attributed to toxic levels of non-esterified fatty acids formed during lysate incubation.
- Lysates showed equal efficacy against BCG, H37Ra, and H37Rv strains.
Conclusions:
- Immune-activated macrophages possess potent antimycobacterial activity.
- Non-esterified fatty acids are key mediators of this activity.
- The capacity for antimycobacterial activity is associated with delayed hypersensitivity and macrophage activation.