Glucose Metabolism of Human Mononuclear Cell Subpopulations

Abstract

SummaryPrevious studies have demonstrated metabolic dysfunction in the mononuclear cells of some children with abnormal cell-mediated immunity. Interpretation of these observations has been complicated by the extreme heterogeneity of cell types examined. The glycolytic metabolism of relatively enriched T-cells, non-T mononuclear cells (NTM), non-T lymphocytes (NTL), and monocytes was studied in an attempt to measure the metabolism of subpopulations of mononuclear cells.Lactate production by monocytes was 11 times greater than that of T-cells and 2% times greater than that of non-T lymphocytes. Exposure to phytohemagglutinin (PHA) stimulated glycolytic metabolism in T-cells but did not stimulate glucose utilization or lactate production in NTM. Even when T-cells were maximally stimulated by PHA, their observed metabolism was still lower than that of NTL. The ATP content of T lymphocytes and NTL was similar and was constant under the conditions of incubation. The initial ATP content of monocytes was higher than that of lymphocytes, and diminished during incubation.Tricarboxylic acid cycle activity did not contribute significantly to ATP synthesis in any of the mononuclear cell subpopulations, under the conditions of incubation used in this study. Significant hexose monophosphate shunt activity was observed in all mononuclear cell types.These studies demonstrate major metabolic differences between mononuclear cell subtypes. Any correlation of metabolic observation with clinical dysfunction of mononuclear cells requires the study of relatively pure cell populations. SpeculationThe reason for increased glycolysis in NTL is obscure. It may imply an immaturity of a portion of those cells, by analogy to the increased glycolytic activity of young erythrocytes. Alternatively, a subset of NTL may require increased ATP synthesis to perform its functions. In order to delineate these possibilities, methods must be developed which will allow the isolation of large numbers of B and Null lymphocytes for metabolic and functional studies.The performance of biologic functions by cells requires the expenditure of energy derived from cellular metabolism. Cellular dysfunction can be correlated with perturbations of energy metabolism by the dysfunctional cell. This correlation has been most strikingly demonstrated in erythrocytes, in which a variety of hemolytic anemias have been correlated with inherited disorders of glycolysis (17). More recent data suggest that the defect in platelets of patients with Wiskott-Aldrich Syndrome may be related to an inborn error of the Krebs Cycle (14).The authors postulated that malfunction of human mononuclear leukocytes might be caused by or associated with disorders of energy metabolism. Several models of cell-mediated immune dysfunction were studied and diminished ATP content in the mononuclear cells of newborn infants (5) and patients with severe malnutrition (4) have been described. Spec*c correlation between a metabolic deficit and a cellular malfunction could not be made because of the heterog...