Dissociation by colchicine of the hexose monophosphate shunt activation from the bactericidal activity of the leukocyte

Abstract

The effect of the in vitro addition of colchicine on various aspects of leukocyte metabolism was investigated. Colchicine in 6 mm 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 mm 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.