title: Inhibition of human NK cell function by valinomycin, a toxin from Streptomyces griseus in indoor air.
abstract: 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.
authors.affiliation: Department of Pathology, Haartman Institute, FIN-00014 University of Helsinki, Finland. auli.paananen@helsinki.fi
authors.forename: A
authors.initials: A
authors.lastname: Paananen
authors.forename: R
authors.initials: R
authors.lastname: Mikkola
authors.forename: T
authors.initials: T
authors.lastname: Sareneva
authors.forename: S
authors.initials: S
authors.lastname: Matikainen
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: I
authors.initials: I
authors.lastname: Julkunen
authors.forename: M S
authors.initials: MS
authors.lastname: Salkinoja-Salonen
authors.forename: T
authors.initials: T
authors.lastname: Timonen
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D020382:Interleukin-18; D014634:Valinomycin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor