LOW GLUTAMINE CONCENTRATIONS INDUCE PHENOTYPICAL AND FUNCTIONAL-DIFFERENTIATION OF U937 MYELOMONOCYTIC CELLS

L-Glutamine is the most abundant free amino acid of the human body and is essential for the culture of many cell types. Clinically, reductio n of glutamine by administration of glutaminase or the use of glutamin e analogs is a common therapy for patients with acute lymphocytic leuk emia. 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 (R-2 = 0.9885, P < 0.0001), increased cell volume (P < 0.01) and the cytopl asm/nuclear ratio, and enhanced the development of vacuoles but did no t influence cell viability. Culturing cells in reduced concentrations of glutamine augmented the percentage of cells expressing CD64 (Fc rec eptor for IgG/Fc gamma RI, P < 0.01), CD11b (complement receptor type 3/CR3, P < 0.001) and CD71 (transferrin receptor, P < 0.05). The perce ntage of U937 cells expressing CD23 (low affinity receptor for IgE/Fc epsilon RII) was increased at low concentrations of glutamine at both the protein (P < 0.01) and mRNA levels. The percentage of U937 cells p hagocytizing opsonized E. coli (P < 0.001) or latex particles (P < 0.0 01) was enhanced by lowering the glutamine concentration. In conclusio n, reducing glutamine concentration causes differentiation of the cell line U937 along the monocytic pathway. These effects may indicate a m echanistic basis for prior published evidence that glutaminase and glu tamine antagonists are effective anti-tumor agents.