Reactive Oxygen Species and Neutrophil Function

Abstract

Neutrophils are essential for killing bacteria and other microorganisms, and they also have a significant role in regulating the inflammatory response. Stimulated neutrophils activate their NADPH oxidase (NOX2) to generate large amounts of superoxide, which acts as a precursor of hydrogen peroxide and other reactive oxygen species that are generated by their heme enzyme myeloperoxidase. When neutrophils engulf bacteria they enclose them in small vesicles (phagosomes) into which superoxide is released by activated NOX2 on the internalized neutrophil membrane. The superoxide dismutates to hydrogen peroxide, which is used by myeloperoxidase to generate other oxidants, including the highly microbicidal species hypochlorous acid. NOX activation occurs at other sites in the cell, where it is considered to have a regulatory function. Neutrophils also release oxidants, which can modify extracellular targets and affect the function of neighboring cells. We discuss the identity and chemical properties of the specific oxidants produced by neutrophils in different situations, and what is known about oxidative mechanisms of microbial killing, inflammatory tissue damage, and signaling.

Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions

“…[15][16][17][18] Moreover, the notion that the Rev1Xpc phenotypes are cell autonomous, combined with the specific depletion of neutrophils (see Figure 2D) that produce high levels of reactive oxygen species (ROS), 30 hinted at helixdistorting oxidative DNA lesions as possible culprits for the Rev1 and Rev1Xpc HSPC phenotypes. The scarcity of long-term Rev1Xpc HSCs precluded their analysis, and therefore, we investigated responses to endogenous oxidative stress in cultured Rev1 single-deficient HSCs.…”

Angiotensin-converting enzyme in innate and adaptive immunity

“…The enclosed bacteria are killed by several different mechanisms, but one of the most powerful is the generation of superoxide (O 2 − ) by NADPH oxidase. O 2 − is then converted to hydrogen peroxide (H 2 O 2 ) and hypochlorous acid (HClO), which are bactericidal 69 . To evaluate whether ACE has a role in O 2 − production, we challenged neutrophils from NeuACE and WT mice with MRSA and found that, although both cell populations had increased O 2 − production, levels from NeuACE cells were >2-fold higher than those from WT cells 68 .…”

Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability

“…hypochlorous acid (HOCl), hypobromous acid (HOBr), hypothiocyanous acid (HOSCN)] and radicals1314. These processes are critical to efficient pathogen killing, but result in significant collateral damage to host tissues15. Oxidant formation can also arise via electron-leakage from mitochondria, from enzymes such as xanthine oxidase and lipoxygenases, and by uncoupling of enzymes such as endothelial and inducible nitric oxide synthases (NOS) (reviewed)8.…”