Respiratory burst
Respiratory burst (or oxidative burst) is the rapid release of the reactive oxygen species (ROS), superoxide anion (O−
2) and hydrogen peroxide (H
2O
2), from different cell types.
This is usually utilised for mammalian
Immunity
Respiratory burst requires a 10 to 20 fold increase in oxygen consumption through NADPH oxidase (NOX2 in humans) activity. NADPH is the key substrate of NOX2, and bears reducing power. Glycogen breakdown is vital to produce NADPH. This occurs via the pentose phosphate pathway.
The NOX2 enzyme is bound in the phagolysosome membrane. Post bacterial phagocytosis, it is activated, producing superoxide via its redox centre, which transfers electrons from cytosolic NADPH to O2 in the phagosome.[2]
2O2 + NADPH —> 2O2•– + NADP+ + H+
The superoxide can then
Pathways for reactive species generation
There are 3 main pathways for the generation of reactive oxygen species or reactive nitrogen species (RNS) in effector cells:[3]
- Superoxide dismutase (or alternatively, myeloperoxidase) generates hydrogen peroxide from superoxide. Hydroxyl radicals are then generated via the Haber–Weiss reaction or the Fenton reaction, of which are both catalyzed by Fe2+.
O2•–+ H2O2 —> •OH + OH– + O2 - In the presence of halide ions, prominently chloride ions, myeloperoxidase uses hydrogen peroxide to produce hypochlorous acid.
H2O2 + Cl− —> ClO− + H2O - Nitric oxide synthase (the inducible isoform, iNOS, in immunity) catalyses the production of nitric oxide from L-arginine. 2L-arginine + 3NADPH + 3 H+ + 4O2 —> 2citrulline + 2NO• + 4H2O + 3NADP+
Nitric oxide may react with superoxide anions to produce peroxynitrite anion.
Defense against pathogens
The exposure to these reactive species in the respiratory burst results in pathology. This is due to oxidative damage to the engulfed bacteria.
Notably, peroxynitrite is a very strong
Hypochlorous acid reacts with a range of biomolecules, including DNA, lipids and proteins. HClO may oxidise cysteines and
Integral to hypochlorous acid formation is myeloperoxidase. Myeloperoxidase is most abundant in neutrophils, wherein phagocytosis is accompanied by degranulation. This is the fusion of granules with the phagolysosome, releasing their contents, including myeloperoxidase.[10] As many microbicidal products are formed during respiratory burst, the importance of individual molecules in killing invading pathogens is not wholly understood.
Due to the high toxicity of generated antimicrobial products including ROS, neutrophils have a short life span to limit host tissue damage during inflammation.
Disease
Cellular signalling
Non-phagocytic cells
In non-phagocytic cells, oxidative burst products are used in intracellular signalling pathways. The generated ROS achieve this via shifting the cell
The NADPH oxidase isoform NOX1 transiently produces a burst of superoxide in response to growth factor (e.g. EGF) stimulation of respective receptors.[13] Superoxide is dismutated to hydrogen peroxide at a rate close to the diffusion-limited rate. This spatial restriction for superoxide‘s dismutation allows for specificity of redox signalling. Specificity is also ensured by NOX1 localisation in specific microdomains in the cell’s plasma membrane. Through channels such as aquaporin or diffusion, hydrogen peroxide enters the cytosol. There, it oxidises the cysteine groups of redox-sensitive proteins, which can then transduce signals.[14]
Macrophages
Oxidative burst in phagocytes is most commonly associated with bacterial killing. However, macrophages, especially alveolar macrophages, usually produce far lower levels of ROS than neutrophils, and may require activation for their bactericidal properties. Instead, their transient oxidative burst regulates the inflammatory response by inducing cytokine synthesis for redox signalling, resulting in an influx of neutrophils and activated macrophages.[15]
Cancer cells
Cancer cells can manipulate cell signalling by producing excess levels of ROS, thereby constitutively activating pathways to promote their cellular growth and proliferation.
Fertilisation
Most notably, oxidative burst post fertilisation can be seen in the sea urchin egg. This is believed to be evolutionally divergent from that in neutrophils.
Hydrogen peroxide is produced by egg oxidase activity following an increase in oxygen consumption.[19] This is essential for the cross-linking of the ovum proteins to prevent lethal polyspermy. Hydrogen peroxide itself is also spermicidal. However, the generated reactive species are maintained at lower levels than in immunity to protect the fertilised egg itself from oxidative damage. This is achieved by the elimination of hydrogen peroxide primarily through the dual function of the same egg oxidase, and secondarily through cytoplasmic ROS scavengers, such as catalase and glutathione.[20]
In plants
Oxidative burst acts as a defence mechanism to pathogen infection in plants. This is seen post
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External links
- Respiratory+burst at the U.S. National Library of Medicine Medical Subject Headings (MeSH)