Glycolysis as an energy source for stimulation of lymphocytes by phytohemagglutinin

Abstract

Various metabolic activities have been measured on cultures of lymphocytes from human blood which have been carefully freed of other types of cells. When these cultures were stimulated with phytohemagglutinin (PHA), a large increase in lactate production occurred which clearly correlated with the synthesis of DNA, RNA, and protein. In contrast, there was no demonstrable change in respiration. Deoxyglucose, which inhibits glycolysis, inhibited all synthetic activity back to the level of cultures not activated with PHA, and arrested the histological development of the cells. The effect of DOG was reversible; if the inhibitor was removed the culture could be activated with a new addition of PHA. Conversely, 2,4-dinitrophenol, which inhibits oxidative phosphorylation, had no effect on DNA synthesis, and only a partial inhibitory effect on RNA and protein synthesis. The lymphocytes continued to develop into blast forms. The results are interpreted as showing that the increased cellular activities following PHA activation are dependent on glycolysis rather than on respiration. This resembles in many respects what occurs in other rapidly dividing cells. The system may therefore be useful for studying metabolic controls associated with differentiation.