Inhibition of human NK cell function by valinomycin, a toxin from Streptomyces griseus in indoor air.
Streptomyces griseus strains isolated from indoor dust have been shown to synthesize valinomycin. In this report, we show that human peripheral blood lymphocytes treated with small doses (30 ng ml(-1)) of pure valinomycin or high-pressure liquid chromatography-pure valinomycin from S. griseus quickly show mitochondrial swelling and reduced NK cell activity. Larger doses (>100 ng/ml(-1)) induced NK cell apoptosis within 2 days. Within 2 h, the toxin at 100 ng ml(-1) dramatically inhibited interleukin-15 (IL-15)- and IL-18-induced granulocyte-macrophage colony-stimulating factor and gamma interferon (IFN-gamma) production by NK cells. However, IFN-gamma production induced by a combination of IL-15 and IL-18 was somewhat less sensitive to valinomycin, suggesting a protective effect of the cytokine combination against valinomycin. Thus, valinomycin in very small doses may profoundly alter the immune response by reducing NK cell cytotoxicity and cytokine production.
Paananen
A
A
Department of Pathology, Haartman Institute, FIN-00014 University of Helsinki, Finland. auli.paananen@helsinki.fi
Mikkola
R
R
Sareneva
T
T
Matikainen
S
S
Andersson
M
M
Julkunen
I
I
Salkinoja-Salonen
M S
MS
Timonen
T
T
D000391:Air Microbiology; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000633:toxicity; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D019409:Interleukin-15 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D008933:Mitochondrial Swelling / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry* / Q000302:isolation & purification; D014634:Valinomycin / Q000302:isolation & purification / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D020382:Interleukin-18; D014634:Valinomycin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor