Inhibition of human natural killer cell activity by cereulide, an emetic toxin from Bacillus cereus.
The lipophilic toxin, cereulide, emitted by emetic food poisoning causing strains of Bacillus cereus, is a powerful mitochondria toxin. It is highly lipophilic and rapidly absorbed from the gut into the bloodstream. We tested how this toxin influences natural killer (NK) cells, which are important effectors in defence against infections and malignancy. Cereulide inhibited cytotoxicity and cytokine production of natural killer cells, caused swelling of natural killer cell mitochondria, and eventually induced natural killer cell apoptosis. The suppressive effect on cytotoxicity was fast and toxic concentration low, 20-30 microg/l. As the emesis causing concentration of cereulide is around 10 microg/kg of total body mass, our results suggest that emesis causing or even lower doses of cereulide may also have a systemic natural killer cell suppressive effect.
Department of Pathology, Haartman Institute, University of Helsinki, Finland. auli.paananen@helsinki.fi
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A
Paananen
R
R
Mikkola
T
T
Sareneva
S
S
Matikainen
M
M
Hess
M
M
Andersson
I
I
Julkunen
M S
MS
Salkinoja-Salonen
T
T
Timonen
D017209:Apoptosis; D001409:Bacillus cereus; D001427:Bacterial Toxins / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D047630:Depsipeptides; D004305:Dose-Response Relationship, Drug; D004639:Emetics / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010456:Peptides, Cyclic / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
D001427:Bacterial Toxins; D016207:Cytokines; D047630:Depsipeptides; D004639:Emetics; D007375:Interleukin-1; D010456:Peptides, Cyclic; C089294:cereulide; D007371:Interferon-gamma