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Infection and Immunity, January 2000, p. 165-169, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Inhibition of Human NK Cell Function by Valinomycin, a Toxin from Streptomyces griseus in Indoor Air

Auli Paananen,1,* Raimo Mikkola,2 Timo Sareneva,3 Sampsa Matikainen,3 Maria Andersson,2 Ilkka Julkunen,3 Mirja S. Salkinoja-Salonen,2 and Tuomo Timonen1

Department of Pathology, Haartman Institute,1 and Department of Applied Chemistry and Microbiology,2 FIN-00014 University of Helsinki, and Department of Virology, National Public Health Institute, FIN-00300 Helsinki,3 Finland

Received 20 August 1999/Returned for modification 30 September 1999/Accepted 18 October 1999

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.

* Corresponding author. Mailing address: Department of Pathology, Haartman Institute, University of Helsinki, POB 21, FIN-00014 University of Helsinki, Finland. Phone: 358 9 19126517. Fax: 358 9 19126675. E-mail: auli.paananen{at}helsinki.fi.

Infection and Immunity, January 2000, p. 165-169, Vol. 68, No. 1
0019-9567/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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