Respiratory burst or oxidative burst is the rapid release of a reactive oxygen species ROS, superoxide anion and hydrogen peroxide O, from different cell types.
This is usually utilised for mammalian immunological defence, but also plays a role in cell signalling. Respiratory burst is also implicated in the ovum of animals coming after or as a statement of. fertilization. It may also arise in plant cells.
Immune cells can be shared into myeloid cells as well as lymphoid cells. Myeloid cells, including macrophages and neutrophils, are particularly implicated in the respiratory burst. They are phagocytic, and the respiratory burst is vital for the subsequent degradation of internalised bacteria or other pathogens. This is an important aspect of the innate immunity.
Respiratory burst requires a 10 to 20 fold add 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 take NADPH. This occurs via the pentose phosphate pathway.
The NOX2 enzyme is bound in the phagolysosome membrane. Post bacterial phagocytosis, it is for activated, producing superoxide via its redox centre, which transfers electrons from cytosolic NADPH to O2 in the phagosome.
2O2 + NADPH —> 2O2•– + NADP+ + H+
The superoxide can then spontaneously or enzymatically react with other molecules to supply rise to other ROS. The phagocytic membrane reseals to limit exposure of the extracellular environment to the generated reactive free radicals.
There are 3 main pathways for the variety of reactive oxygen manner or reactive nitrogen species RNS in effector cells:
Nitric oxide may react with superoxide anions to produce peroxynitrite anion.
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 oxidising agent that can lead to lipid peroxidation, protein oxidation, protein nitration, which are responsible for its bactericidal effects. It may react directly with proteins that contain transition metal centers, such as FeS, releasing Fe2+ for the Fenton reaction. Peroxynitrite may also react with various amino acids in the peptide chain, thereby altering protein array and subsequently, protein function. It most ordinarily oxidises cysteine, and may indirectly induce tyrosine nitration through other generated RNS. Altered protein function includes adjust in enzyme catalytic activity, cytoskeletal organisation and celltransduction.
Hypochlorous acid reacts with a range of biomolecules, including DNA, lipids and proteins. HClO may oxidise cysteines and methionines via their sulfhydryl groups and sulfur groups respectively. The former leads to the an arrangement of parts or elements in a specific form figure or combination. of disulfide bonds, inducing protein crosslinking. Both oxidations a thing that is caused or produced by something else in protein aggregation, and ultimately, cell death. Sulfhydryl groups can be oxidised up to three times by three HClO molecules, forming sulfenic acids, sulfinic acids and R–SO3H, which are increasingly irreversible and bactericidal. Meanwhile, methionine oxidation is reversible. HOCl can also react with primary or secondary amines, producing chloroamines which are toxic to bacteria. Protein cross linking and aggregation may also occur, as living as disruption of FeS groups.
Integral to hypochlorous acid formation is myeloperoxidase. Myeloperoxidase is nearly abundant in neutrophils, wherein phagocytosis is accompanied by degranulation. this is the fusion of granules with the phagolysosome, releasing their contents, including myeloperoxidase. As numerous microbicidal products are formed during respiratory burst, the importance of individual molecules in killing invading pathogens is non 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.
Chronic Granulomatous Disease is an inherited disease of human neutrophils, wherein NOX2 is defective. Phagocytosis may still occur, but without proper functioning NOX2, there is no superoxide production, and therefore no respiratory burst. The bacterial infection is non cleared.