Effect of D-glucosamine on human natural killer activity in vitro

D-Glucosamine has been shown in animal studies to have selective tumoricidal activity. In human cancer patients, preliminary data indicate that natural killer (NK) activity is increased secondary to D-glucosamine infusion. The present study examined the effect of D-glucosamine on several in vitro indices of human immune responsiveness including NK cell activity and T and B cell mitogenesis. NK activity in normal human peripheral blood mononuclear cells was significantly elevated in the presence of 10(-4) and 5 X 10(-4) M D-glucosamine. The increment in NK activity was mediated by nonadherent effector cells and was not due to an increased susceptibility of target cells. Analysis by single-cell assay indicated that the number of effector/target conjugates was not increased but that there was increased lytic activity of the NK cells. Previous studies from our laboratory indicated that several drugs which perturb thymidine (TdR) metabolism were effective in enhancing the in vitro NK activity. As D-glucosamine has been observed to alter cellular pyrimidine nucleotide pools and TdR metabolism in tumor cells, the effect of exogenous TdR was assessed on D-glucosamine-stimulated NK activity. Exogenous TdR inhibited D-glucosamine-induced augmentation of NK activity in a dose-dependent manner and completely abrogated the drug response at 10(-7) M. Similar experiments indicated that TdR did not affect the interferon-induced augmentation of NK activity in concentrations up to 10(-4) M. Although human NK activity was enhanced by D-glucosamine in vitro, there was no change induced in T or B lymphocyte mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)