Suppression of human natural killer cell activity by amino sugars.
In the present study we investigated the effect of amino sugars on human natural killer (NK) activity against K562, a human myeloid leukemia cell line, and Molt-4, a human T lymphoma cell line. The presence of amino sugars such as D-mannosamine, D-galactosamine, and D-glucosamine [6-25 mM (in the case of D-mannosamine, 1.5-12.5 mM)] in a 4-hr chromium-51 (Cr) release assay significantly inhibited NK activity of large granular lymphocytes (LGL) without affecting effector cell viability or spontaneous release from target cells. Sugars with acetylated amino residues (N-acetyl-D-mannosamine, N-acetyl-D-galactosamine, and N-acetyl-D-glucosamine) showed much smaller NK inhibition. Among the amino sugars tested, D-mannosamine was the strongest suppressor. When either LGL or K562 cells were pretreated with amino sugars and used in the 4-hr 51Cr release assay, only the pretreatment of effector cells resulted in the reduction of NK activity. The binding capacity of LGL to K562 cells, determined by a conjugate assay, was not reduced by the amino sugars enough to explain the strong inhibition of NK activity by these amino sugars, although some inhibitory effect on the binding of LGL to K562 cells was observed in some cases. In contrast, the polarization of the effector cell cytoskeleton, one of the energy-dependent steps, was significantly impaired. The cellular ATP level of LGL was also significantly reduced and the reduction of cellular ATP correlated well with the degree of the inhibition of NK cytotoxicity. These results suggest that the suppression of NK activity by amino sugars is due to the reduction of the ATP-based energy supply of the effector cells and that amino sugars, especially D-mannosamine, should be recognized as potent suppressors of natural cell-mediated immunity.
Yagita
M
M
Department of Pathology, University of Helsinki, Finland.
Nakajima
M
M
Saksela
E
E
D000255:Adenosine Triphosphate / Q000032:analysis; D000606:Amino Sugars / Q000494:pharmacology*; D003599:Cytoskeleton / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000032:analysis / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000606:Amino Sugars; D000255:Adenosine Triphosphate; D005947:Glucose