The in vitro influence of glucose, fructose, and insulin on human leukocytes of healthy and diabetic subjects was measured as a part of a study of the metabolic behavior of these cells, and an attempt was made to correlate metabolic alterations in leukocytes with resistance and susceptibility to infectious diseases. Previous workers have shown that leukocytes from alloxan diabetic rabbits are able to phagocytize but not destroy bacteria (1). Dubos has shown that lactate in the presence of low oxygen tension is bactericidal for M. tuberculosis (2). Human leukocytes produce lactic acid in the presence of oxygen, and the quantity is not changed markedly by decreased oxygen tension (3, 4). It has also been shown that these cells produced more lactate from glucose than from fructose, and that when the two sugars were added simultaneously the lactate production was additive. The effect of these hexoses and insulin was studied on leukocytes from normal and diabetic subjects. The responses after cell injury were also determined.
METHODSHealthy subjects and subjects with moderately severe untreated diabetes mellitus were used as donors. The obese mild diabetics were excluded from this series. The blood was collected before breakfast. The white
The carbohydrate metabolism of the polymorphonuclear leukocyte has been reviewed recently by Beck and Valentine' and will be only briefly summarized because of the completeness of this review. The cardinal feature of the metabolism of this cell is its high perobic lactic acid production, which is not influenced by oxygen s There is, an active oxygen consumption and indications that there is an intact Krebs cycle.ls.s The mature polymorphonuclear leukocyte contains glycogen.' Wagner and hi4 co-workers have shown that this glycogen is utilized to produce reducing and nonreducing intermediates of carbohydrate metabolism by phosphorylase activity.6-Glucose 1-phosphate, fructose &phosphate, fructose 1,6-diphosphate, and phosphoglyceric acid have been isolated.? The studies isolating these compounds have shown the existence of phosphorylase, phosphoglucomutase, and phosphohexoisomerase activity, and have indicated, as well, the presence of triose phosphate dehydrogenase. This group has also shown the existence of hexokinase in the insoluble particles of the ce11.8The present study was undertaken to determine some of the physiological aspects of leukocyte metabolism and to correlate these aspects with reactions in disease, Emphasis was placed on the reaction of the intact cell to various environmental changes.
MethodsBlood was collected from the cubital vein of various subjects into a nonwetting system consisting of either siliconed syringes or a Fenwal blood pack. 0 An ion exchange resin (Dowex 50) in the blood pack or heparin (0.02 mgm./ml.) were used as an anticoagulant. Sedimentation was accomplished by the use of nonpyrogenic dextranll in a final concentration of 1 per cent. The platelets, white cells, and plasma were separated by centrifugation for 15 minutes at 50 X g. The resulting sediment contained 90 to 95 per cent polymorphonuclear leukocytes and a red to white cell ratio of from 10 to 1 to as low as 1 to 1. The cells were resuspended in a modification of Hank's solution.a The concentrations were adjusted to 30 million cells per ml. before final study. With manometric studies a total of 90 million cells were used. The cell number is critical, since it influences the rates of respiration and glycolysis. The
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