Respiratory burst in phagocytes

Nitric oxide and eicosanoid synthesis haem synthesis. The importance of the pentose phosphate pathway reduced glutathione in maintaining red cell integrity. The respiratory burst in phagocytes. Clotting and complement enzyme cascades. Metabolism of lipoproteins. 

Figure 14.2 The respiratory burst in phagocytes kills bacteria.

Baggiolini, M. and Thelen, M. (1991). The phagocytes and the respiratory burst. In Oxidative Stress (ed. H. Sies) pp. 399-420. Academic Press, London. 

Principle The respiratory burst of phagocytic cells can be assessed by incubating a suspension of the cells in an isotonic solution of the yellow oxidised nitroblue tetrazolium (NBT) dye. During this process, the soluble dye interacts with the cytoplasmic components associating with the oxidant species generated. Although the NBT test is not a specific marker for superoxide production, NBT reduction by activat-... 

Benov, L. and Fridovich, I. (1996). Elscherichia coli exhibits negative chemotaxis in gradients of hydrogen peroxide, hypochlorite, and Ai-chlorotaurine Products of the respiratory burst of phagocytic cells. Proc. Natl. Acad. Sd. U.S.A. 93,... 

All these factors may exert their toxic effects on the lungs. The oxidant gases in the atmosphere, cigarette smoke, and the respiratory burst of phagocytes in the... 

It was found that POP induces hemolysis of erythrocyte," modifies the respiratory burst of phagocytes, and increases the permeabihty of their membranes." Chemically oxidized or photooxidized psoralens inhibit chemotactic activity of polymorphonucleate cells, and induce mutagenic and lethal effects in the microorganism. ... 

In addition to the well-characterized role of iron in catalysing redox interactions, other metallic contaminants, for example, nickel, may also contribute. In vivo toxicity studies have demonstrated the capacity of nickel particulate compounds to induce tumours following intraperitoneal injection (Pott etal., 1987). Such activity is proportional to their phagocytic uptake, and to the associated respiratory burst and generation of PMN-derived reactive oxygen metabolites (ROMs), a proposed pathogenic mechanism (Evans et al., 1992a). 

At the same time the interaction of superoxide with MPO may affect a total superoxide production by phagocytes. Thus, the superoxide adduct of MPO (Compound III) is probably quantitatively formed in PMA-stimulated human neutrophils [223]. Edwards and Swan [224] proposed that superoxide production regulate the respiratory burst of stimulated human neutrophils. It has also been suggested that the interaction of superoxide with HRP, MPO, and LPO resulted in the formation of Compound III by a two-step reaction [225]. Superoxide is able to react relatively rapidly with peroxidases and their catalytic intermediates. For example, the rate constant for reaction of superoxide with Fe(III)MPO is equal to 1.1-2.1 x 1061 mol 1 s 1 [226], and the rate constants for the reactions of Oi and HOO with HRP Compound I are equal to 1.6 x 106 and 2.2 x 1081 mol-1 s-1, respectively [227]. Thus, peroxidases may change their functions, from acting as prooxidant enzymes and the catalysts of free radical processes, and acquire antioxidant catalase properties as shown for HRP [228] and MPO [229]. In this case catalase activity depends on the two-electron oxidation of hydrogen peroxide by Compound I. 

Low levels of mercuric chloride in polymorphonuclear cells may profoundly alter the cell respiratory burst, measured as chemiluminiscence, oxygen consumption and H2Oz production [171-173], depress phagocytic capacity [172, 173] and enhance release of lysosomal enzymes [ 172] with minimal loss of cell viability. A stimulation of oxygen metabolism in vivo might promote tissue injury, via the local production of free oxygen metabolites, in addition to depression of host defence [173],... 

Before we discuss how neutrophils (and other professional phagocytes) generate O2 and other oxygen metabolites during the respiratory burst, let us first consider why they produce such compounds. If these metabolites are produced in order to kill phagocytosed microorganisms, why and how are they toxic The answer comes from an examination of the chemistry of the oxygen molecule itself. 

In the early 1960s in Japan, a b-type cytochrome was found in horse neutrophils and, because it bound CO, it was proposed to be functional during the respiratory burst. This work went largely unnoticed, but in 1978 Segal and Jones in the United Kingdom discovered that a b-type cytochrome became incorporated into phagolysosomes furthermore, this cytochrome was absent in some patients with CGD. These workers correctly proposed that it was a key component of the NADPH oxidase. This cytochrome was a landmark discovery in phagocyte research for a number of reasons ... 

IFN-y also induces the costimulatory molecules on the macrophages, which increases cell-mediated immunity. As a consequence, there is activation and increase in the tumoricidal and antimicrobial activity of mononuclear phagocytes, granulocytes and NK cells. The activation of neutrophils by IFN-y includes an increase in their respiratory burst. IFN-y stimulates the cytolytic activity of NK cells. It is an activator of vascular endothelial cells, promoting CD4+ T lymphocyte adhesion and morphological alterations, which facilitates lymphocyte extravasation. IFN-y promotes opsonization by stimulating the production of IgG subclasses that activate the complement pathway. A summary of the characteristics of selected cytokines is shown in Table 2.3. 

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