PMID: 17278388Feb 7, 2007

How superoxide production by neutrophil leukocytes kills microbes

Novartis Foundation Symposium
Anthony W Segal

Abstract

Neutrophils represent the primary innate immune response to infection by bacteria and fungi which they ingest, kill and digest. Killing and digestion are dependent upon oxygen consumption by the NADPH oxidase which generates superoxide (O2-) in the phagocytic vacuole. Killing was thought to occur by free radical reactions of reactive oxygen species (ROS) with the microbes, or through the generation of HOCI by myeloperoxidase acting on H2O2. However, in knockout mice lacking the neutral proteases cathepsin G and elastase, these ROS do not kill microbes despite normal production of oxygen free radicals and halogenation. It turns out that the oxidase has another function. The passage of electrons is electrogenic and the charge generated across the wall of the phagocytic vacuole must be compensated if electron transport is to continue. This compensation is largely accomplished by the passage of Cl-, which enters the vacuole from the granules, where it is present at a concentration of about 500mM, into the cytosol. The pH of the vacuole is regulated by a Na+/H+ exchanger, NHE1, which pumps Na+ out of the vacuole in exchange for cytosolic H+ together with a flux of K+ into the vacuole through the BKCa channel. These ion fluxes and pH...Continue Reading

Related Concepts

Immune Response
NHE1 Antiporter
Neutrophil Band Cells
Hydrogen Peroxide
Elastases
SLC9A1 gene
Enzymes, antithrombotic
Cathepsin G
Peptide Hydrolases
Filamentous fungus

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