Inhibition of human NK cell function by valinomycin, a toxin from Streptomyces griseus in indoor air

A Paananen*, R Mikkola, T Sareneva, S Matikainen, M Andersson, Petro Julkunen, MS Salkinoja-Salonen, T Timonen

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)165-169
Number of pages5
JournalINFECTION AND IMMUNITY
Volume68
Issue number1
Publication statusPublished - Jan 2000
MoE publication typeA1 Journal article-refereed

Keywords

  • NATURAL-KILLER-CELLS
  • HUMAN T-CELLS
  • DNA FRAGMENTATION
  • INTERFERON-GAMMA
  • APOPTOSIS
  • CALCIUM
  • INTERLEUKIN-15
  • CYTOTOXICITY
  • LYMPHOCYTES
  • ACTIVATION

Cite this