Dissociation by Colchicine of the Hexose Monophosphate Shunt Activation from the Bactericidal Activity of the Leukocyte

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Abstract
The effect of the in vitro addition of colchicine on various aspects of leukocyte metabolism was investigated. Colchicine in 6 m m concentration reduced the oxygen uptake of phagocytizing leukocytes to below the level of resting cells. A similar concentration of colchicine inhibited the increase in glucose- 1 - 14 C oxidation by 90% and the quantitative nitroblue tetrazolium reduction by about 50%. Experiments with broken cell preparations indicate that the inhibition of the hexose monophosphate shunt is due to an inhibition of the activity of the shunt enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. In spite of these pronounced metabolic changes, the addition of 6 m m colchicine had no observable effect on the bactericidal activity of the leukocyte against three test organisms. These results support a mechanism for phagocytosis in which the hexose monophosphate-shunt activation is a secondary phenomenon which is not required for the actual killing process.