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Recombinant Granulocyte–Macrophage Colony‐Stimulating Factor Activates Human Macrophages to Inhibit Growth or Kill Mycobacterium avium Complex
Author(s) -
Bermudez Luiz Eduardo M.,
Young Lowell S.
Publication year - 1990
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.48.1.67
Subject(s) - biology , intracellular , recombinant dna , microbiology and biotechnology , macrophage , monocyte , granulocyte macrophage colony stimulating factor , interferon gamma , colony stimulating factor , intracellular parasite , macrophage colony stimulating factor , cytokine , tumor necrosis factor alpha , immunology , in vitro , biochemistry , gene , stem cell , haematopoiesis
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 (10–10 4 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 (10 2 U/ml) plus TNF (10 2 U/ml) augmented macrophage killing (range, 31 ± 4%) compared with GM‐CSF (10 2 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.