Inhibition of human natural killer activity by lysosomotropic agents.
We have examined the effect of three lysosomotropic amines on human NK cell activity. Dansylcadaverine (DCA), diphenylamine (DPA), and lidocaine (LID) inhibited NK activity of nylon wool-purified and large granular lymphocyte (LGL)-enriched cell preparations. Cadaverine (CAD), an analog of DCA that does not affect lysosomal function, had no effect on NK activity. Binding of the K562 target cells to effector cells, as assessed in a single cell assay, was not inhibited by DCA, DPA, or LID. Cytotoxicity was inhibited by DCA and DPA only when these drugs were added within 5 min after the initiation of NK assays. In contrast, LID inhibited NK activity even when added 60 min after the addition of effector cells to target cells. All three amines that inhibited NK activity also reduced the intracellular concentration of the lysosomal enzyme beta-glucuronidase without affecting the activity of the cytoplasmic enzyme lactate dehydrogenase. Kinetic analysis revealed that LID inhibited both the maximum velocity (Vmax) of the cytotoxicity reaction as well as the affinity constant (Km); whereas DCA and DPA only inhibited Vmax.
D000328:Adult; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004159:Diphenylamine / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology
D007166:Immunosuppressive Agents; D008012:Lidocaine; D004159:Diphenylamine; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; C008542:monodansylcadaverine; D002103:Cadaverine