The increased respiration of phagocytes during phagocytosis was discovered in 1933 by Baldridge and Gerard,1 who measured a small but significant increase in the oxygen consumption by canine neutrophils during phagocytosis of bacteria. This enhanced metabolic response of the neutrophils was initially attributed to an increased generation of mitochondrial energy to meet the needs of the phagocytic process, and it was not realized until 1959 that this increase in respiration was due to nonmitochondrial activity. The studies by Sbarra and Karnovsky2 clearly established that this respiratory burst of phagocytosis is insensitive to mitochondrial inhibitors and that the energy needed for phagocytosis by neutrophils is provided by glycolysis. It was later shown that consumption of ATP from a pool that is apparently not regained3, 4 also adds significantly to the energy expenditure during ingestion of particles by neutrophils. In macrophages, the energy for the phagocytic process is partially provided by creatine phosphate, which may ultimately be regained from oxidative metabolism.5 Although different phagocytic cells may provide the extra energy needed for phagocytosis by activating different biochemical pathways, all phagocytes—neutrophils,6,7monocytes,8,9 eosinophils,10, 11 and lung12 and peritoneal macrophages6,7,13—mount a nonmitochondrial respiratory burst during phagocytosis due to activation of a unique biochemical entity, the membrane-bound NADPH oxidase. It has further been shown that the oxidase may be activated secondary to stimulation of the phagocytes with a wide variety of stimuli that act through binding to receptors other than the Fc and C3b receptors that mediate phagocytoses. These stimuli include N-formyl-methionyl-leucyl-phenylalanine (fMPL),14 phorbol myristate acetate (PMA),15 A 23187,16 concanavalin A (Con A),17 and others.


NADPH Oxidase Human Neutrophil Respiratory Burst Chronic Granulomatous Disease Phorbol Myristate Acetate 
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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Niels Borregaard
    • 1
  1. 1.Department of Medicine and Hematology C, Gentofte HospitalUniversity of CopenhagenHellerupDenmark

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