Chapter 33 : The NADPH Oxidase and Microbial Killing by Neutrophils, With a Particular Emphasis on the Proposed Antimicrobial Role of Myeloperoxidase within the Phagocytic Vacuole

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In 1933, Baldridge and Gerard observed the “extra respiration of phagocytosis” when dog leukocytes were mixed with Gram-positive bacteria and assumed that it was associated with the production of energy required for engulfment of the organisms. It was later shown that this “respiratory burst” was not inhibited by the mitochondrial poisons cyanide ( ) or azide ( ), which indicated that this is a nonmitochondrial process. The hunt for the neutrophil oxidase was then on because oxidative phosphorylation is far and away the major mechanism by which oxygen is consumed in mammalian cells, and another system that could consume oxygen at a similar rate was of considerable interest. Although many oxidases use NADH or NADPH as substrate, this oxidase was specifically called the NADPH oxidase because in the early days there was quite a controversy as to whether the substrate was NADH ( ) or NADPH ( ), and the matter was finally settled in favor of NADPH.

Citation: Levine A, Segal A. 2017. The NADPH Oxidase and Microbial Killing by Neutrophils, With a Particular Emphasis on the Proposed Antimicrobial Role of Myeloperoxidase within the Phagocytic Vacuole, p 599-613. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0018-2015
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Figure 1

Time courses of changes in vacuolar pH in human and and wild-type (WT) mouse neutrophils phagocytosing SNARF-labeled . Reprinted from reference , with permission.

Citation: Levine A, Segal A. 2017. The NADPH Oxidase and Microbial Killing by Neutrophils, With a Particular Emphasis on the Proposed Antimicrobial Role of Myeloperoxidase within the Phagocytic Vacuole, p 599-613. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0018-2015
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Image of Figure 2
Figure 2

Schematic representation of the neutrophil phagocytic vacuole showing the consequences of electron transport by NOX2 onto oxygen. The proposed ion fluxes that might be required to compensate the movement of charge across the phagocytic membrane together with modulators of ion fluxes are shown. CCCP, carbonyl cyanide m-chlorophenyl hydrazone; NHE, sodium proton exchanger. Reprinted from reference , with permission.

Citation: Levine A, Segal A. 2017. The NADPH Oxidase and Microbial Killing by Neutrophils, With a Particular Emphasis on the Proposed Antimicrobial Role of Myeloperoxidase within the Phagocytic Vacuole, p 599-613. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0018-2015
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Figure 3

The effect of variations in pH on peroxidatic (TMB and o-Dianisidine) and chlorinating monochlorodimedone (MCD) activities of MPO and on the protease activities of cathepsin G and of elastase are shown. TMB, tetramethylbenzidine. From Levine et al. ( ).

Citation: Levine A, Segal A. 2017. The NADPH Oxidase and Microbial Killing by Neutrophils, With a Particular Emphasis on the Proposed Antimicrobial Role of Myeloperoxidase within the Phagocytic Vacuole, p 599-613. In Gordon S (ed), Myeloid Cells in Health and Disease. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MCHD-0018-2015
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