The respiratory burst of phagocytic cells is associated with a rise in vacuolar pH

AW Segal, M Geisow, R Garcia, A Harper, R Miller - Nature, 1981 - nature.com
AW Segal, M Geisow, R Garcia, A Harper, R Miller
Nature, 1981nature.com
Neutrophil leukocytes are the body's major defence against bacteria, which they
phagocytose and kill. It has been found that phagocytosis and killing are accompanied by a
dramatic rise in non-mitochondrial respiration1, 2; and that the efficiency of killing is
impaired in the absence of oxygen3, 4. It is also impaired in neutrophils from patients with
chronic granulomatous disease (CGD), where the respiratory burst is absent5. This has
been difficult to reconcile with their normal content of granule proteins that kill bacteria in …
Abstract
Neutrophil leukocytes are the body's major defence against bacteria, which they phagocytose and kill. It has been found that phagocytosis and killing are accompanied by a dramatic rise in non-mitochondrial respiration1,2; and that the efficiency of killing is impaired in the absence of oxygen3,4. It is also impaired in neutrophils from patients with chronic granulomatous disease (CGD), where the respiratory burst is absent5. This has been difficult to reconcile with their normal content of granule proteins that kill bacteria in vitro6. Indeed, CGD cells are essentially normal both morphologically and constitutionally7,8 except that they lack a functional very low potential cytochrome b (b−245)9 which is a component of the oxidase system responsible for the respiratory burst of normal cells10,11. Activation of the oxidase is associated with the generation of various reduced oxygen species12–16 which have been widely thought to be responsible for the killing of phagocytosed microorganisms either directly17, or by acting as substrates for myeloperoxidase-mediated halogenation18. We report here, however, that a major consequence of the defective function of this oxidase in neutrophils and monocytes from CGD patients is an absence of the normal initial rise, and an unusually rapid and extensive fall in pH which is itself associated with the impairment of the killing and digestion of intracellular staphylococci.
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