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The Journal of Nutrition Vol. 127 No. 11 November 1997, pp. 2151-2157
Copyright ©1997 by the American Society for Nutritional Sciences

Low Glutamine Concentrations Induce Phenotypical and Functional Differentiation of U937 Myelomonocytic Cells

Andreas Spittler*, dagger , , Rudolf Oehler*, Peter Goetzinger*, Susanne Holzer*, Carmen M. Reissner*, Fritz Leutmezerdagger , Veronika Rath*, Fritz WrbaDagger , Reinhold Fuegger*, George Boltz-Nitulescudagger , and Erich Roth*

*  Department of Surgery, Research Laboratories, dagger  Institute of General and Experimental Pathology and Dagger  Institute of Clinical Pathology, University of Vienna, 1090 Vienna, Austria

L-Glutamine is the most abundant free amino acid of the human body and is essential for the culture of many cell types. Clinically, reduction of glutamine by administration of glutaminase or the use of glutamine analogs is a common therapy for patients with acute lymphocytic leukemia. In the current study, we investigated the influence of glutamine concentrations on the human myelomonocytic cell line U937. Decreasing the glutamine concentration evoked a reduction in DNA synthesis (R2 = 0.9885, P < 0.0001), increased cell volume (P < 0.01) and the cytoplasm/nuclear ratio, and enhanced the development of vacuoles but did not influence cell viability. Culturing cells in reduced concentrations of glutamine augmented the percentage of cells expressing CD64 (Fc receptor for IgG/Fcgamma RI, P < 0.01), CD11b (complement receptor type 3/CR3, P < 0.001) and CD71 (transferrin receptor, P < 0.05). The percentage of U937 cells expressing CD23 (low affinity receptor for IgE/Fcepsilon RII) was increased at low concentrations of glutamine at both the protein (P < 0.01) and mRNA levels. The percentage of U937 cells phagocytizing opsonized E. coli (P < 0.001) or latex particles (P < 0.001) was enhanced by lowering the glutamine concentration. In conclusion, reducing glutamine concentration causes differentiation of the cell line U937 along the monocytic pathway. These effects may indicate a mechanistic basis for prior published evidence that glutaminase and glutamine antagonists are effective anti-tumor agents.

Key words: glutaminase, acute leukemia, cell volume, monocytic pathway, anti-tumor.




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Copyright © 1997 by American Society for Nutrition