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The rapid production of ROS in activated neutrophils, which requires increased pentose cycling, and thus increased G6PD activity, acts to promote NETosis via oxidative inhibition of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) ( Overall, the uniquely rapid need for neutrophil effector functions, such as NETosis, phagocytosis and degranulation, to be mobilized quickly in the innate immune response necessitates brisk production of NADPH, which is chiefly controlled by the PPP rate-limiting activity of G6PD
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