Recombinant granulocyte-macrophage colony-stimulating factor activates human macrophages to inhibit growth or kill Mycobacterium avium complex

• Published in: Journal of leukocyte biology 1990-07, Vol.48 (1), p.67-73
• Main Authors: Bermudez, Luiz Eduardo M., Young, Lowell S.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Analysis of the immune response. Humoral and cellular immunity; Biological and medical sciences; Cell Survival - drug effects; Cell Survival - physiology; Colony-Stimulating Factors - pharmacology; cytokines; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Inhibitors; Growth Substances - pharmacology; Humans; Immunobiology; Interferon-gamma - pharmacology; intracellular killing; Macrophage Activation - drug effects; Macrophage Activation - physiology; Macrophages - drug effects; Macrophages - physiology; Miscellaneous; Mycobacterium avium Complex - drug effects; Mycobacterium avium Complex - immunology; opportunistic infection; Phagocytosis - drug effects; Phagocytosis - physiology; recombinant human interferon‐gamma (IFNγ); recombinant human tumor necrosis factor (TNF); Recombinant Proteins - pharmacology; Regulatory factors and their cellular receptors; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.48.1.67

Organisms belonging to the Mycobacterium avium complex (MAC) are associated with life‐threatening bacteremia in patients with the acquired immunodeficiency syndrome (AIDS). As these organisms survive within macrophages, we examined the ability of recombinant human granulocyte–monocyte colony‐stimulating factor (GM‐CSF) to activate human monocyte‐derived macrophages to inhibit the intracellular growth or kill the most mouse‐virulent MAC strain In our collection that belongs to serotype 1. While unstimulated cells did not inhibit intracellular growth of MAC, macrophages activated by GM‐CSF (10–104 U/ml) inhibited or killed up to 58 ± 5% of the initial inoculum. This activation was dose‐dependent, with maximal change occurring with a dose of 100 U/ml after 72 hr exposure. Inhibition or killing was demonstrated if GM‐CSF was given both before or after establishment of infection. The combination of GM‐CSF (102 U/ml) plus TNF (102 U/ml) augmented macrophage killing (range, 31 ± 4%) compared with GM‐CSF (102 U/ml) alone, but the combination of recombinant human interferon‐gamma (IFNγ) plus GM‐CSF resulted in a significant decrease in intracellular inhibition of growth or killing (13.3 ± 2%) compared with 57.7 ± 5% obtained with GM‐CSF alone. These results indicate that: 1) GM‐CSF can activate macrophages to inhibit intracellular growth or kill MAC; 2) killing may be augmented by TNF; and 3) IFNγ may impair GM‐CSF‐dependent macrophage activation.