The Respiratory Burst of Neutrophils

The dissociation rate of heme from methemoglobin and consequent formation of the heme-hemopexin complex is facile at 37°C, and the presence of small amounts of H2O2 (even below levels obtained from the respiratory burst of neutrophils) dramatically increases heme dissociation from oxyhemoglobin (55). The binding of heme by hemopexin prevents the oxidation of lipoprotein (50,55,56) and lipid and membrane damage (57-59). 

The effect with which PPT modulate the response of platelets is also pertinent to vascular disease, in particular, thrombosis. Resting platelets inhibit the respiratory burst of neutrophils whereas thrombin-activated platelets increase the respiratory burst. Quercetin and resveratrol at picomolar concentrations attenuate this response by preserving endothelial CD39/ATP-dase," " and on present evidence (see above) such concentrations might be achieved locally following deglucuronidation at a site of inflammation. 

Z5. Zgliczynski, M. J., and Stelmaszynska, T., The respiratory burst of neutrophilic granulocytees and its influence on infected tissues. In Respiratory Burst and Its Physiological Significance, pp. 315-347. Plenum Press, New York, 1972. 

The respiratory burst of neutrophils when they come into contact with foreign particles (see Section 2.4.1). 

S-glutathionylation is defined as a condition when the thiol is GSH. Due to the fact that GSH represents 95% of free intracellular thiols, S-glutathionylation is actually the most important reversible modification of the Cys residue of a protein structure. Such a phenomenon is observed during the respiratory burst of neutrophils and in cells exposed to oxidants. 

Given the toxicity of ROS, it would have been remarkable if they had not been exploited to do intentional damage in some biological context. Indeed, the respiratory burst of neutrophils and macrophages is a crucial element of our antimicrobial arsenal. Superoxide is produced by NADPH oxidase of activated phagocytic cells and can account for up to 90% of their O2... 

Heinecke JW The respiratory burst of neutrophils Oxidative pathways for the initiation of tissue damage at sites of inflammation in Gabrilovich DI (ed) New Outlook for Old Cells. London, Imperial College Press, 1999, pp 31-57. 

Corbett MD, Corbett BR, Hannothiaux MH, Quintana SJ. The covalent binding of acetaminophen to cellular nucleic acids as the result of the respiratory burst of neutrophils derived from the HL-60 cell line. Toxicol Appl Pharmacol 1992 113 (l) 80-86. 

Bass, DA, McPhail, LC, Schmitt, ID, Morris-Natschke, S, McCall, CE and Wykle, RL (1988) Selective priming of rate and duration of the respiratory burst of neutrophils by 1,2-diacyl and 1 -O-alkyl-2-acyl diglycerides. Possible relation to effects on protein kinase C. Journal of Biological Chemistry, 263, 19610-19617. 

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. 

C5a and C5a des Arg stimulate aerobic glycolysis, hexose monophosphate shunt activity, glucose uptake and the respiratory burst of human neutrophils. All of these processes are stimulated in neutrophil suspensions incubated in the absence of cytochalasin B, but the responses are considerably enhanced if this inhibitor of microtubule assembly is present. Stimulated rates of oxidative metabolism are maximal within 2 min of addition of peptides, with half-maximal responses obtained at 30-60 nM C5a and 1-3 pM C5a des Arg. 

Additionally, the myeloperoxidase system even regulates the duration of the respiratory burst because neutrophils from patients with myeloperoxidase deficiency (see 8.3) generate more reactive oxidants than control cells. Also, when myeloperoxidase is inhibited with a specific antibody or a specific inhibitor such as salicylhydroxamic acid, the duration of the respiratory burst, but not the maximal rate of oxidant production, is extended. This indicates that a product of the myeloperoxidase system inhibits the NADPH oxidase and so self-regulates reactive oxidant production during inflammation. 

Garcia, R. C., Segal, A. W. (1988). Phosphorylation of the subunits of cytochrome b. 245 upon triggering of the respiratory burst of human neutrophils and macrophages. Biochem. J. 252, 901-4. 

Carreras, M. C., Pargament, G. A., Catz, S. D., Poderoso, J. J., and Boveris, A. (1994b). Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxy-nitrite during the respiratory burst of human neutrophils. FEBS Lett. 341, 65-68. 

IL-17 induces the production of IL-8 in endothelial and parenchymal cells, indicating an indirect role in PMN recruitment. IL-8 is a potent chemoattractant for polymorphonuclear neutrophils (PMN) and can also stimulate the release of neutrophil granules and the respiratory burst of these cells [5,71-78]. In their study, Kostulas et al. found that the proinflammatory cytokine IL-17 was elevated systemically after ischemic stroke. IL-17 induces the secretion of cytokines, including IL-8, and enhances the expression of ICAM-1 in cultures of stromal cells and human fibroblasts [5,77,79]. 

Jaeger K, Scheinichen D, Heine J, Andre M, Bund M, Piepenbrock S, Leuwer M. Remifentanil, fentanyl, and alfentanil have no influence on the respiratory burst of human neutrophils in vitro. Acta Anaesthesiol Scand 1998 42 1110-3. 

IP Wang, SL Ranng, MF Hsn, CC Chen. Inhibition by gomisin C (a hgnan from Schizandra chinensis) of the respiratory burst of rat neutrophils. Br J Pharmacol 113 945-953, 1994. 

Gomisin C has an inhibitory effect on the respiratory burst of rat neutrophils in vitro [243], The mechanism of action may be mediated partly by the suppression of NADPH oxidase and partly by the decrease in cytosolic Ca2+ released from an agonist-sensitive intracellular store. In fact, gomisin C attenuated the activity of TPA-activated neutrophil particulate NADPH oxidase in a concentration-dependent manner and reduced the increase in cytosolic free Ca2+ in neutrophils stimulated by fMLP in presence or absence of ethylenediaminetetraacetic acid (EDTA). In addition, this study suggests that the gomisin C mechanism is not mediated by changes in cellular cAMP or in inositol phosphates, or by scavenging... 

Lucas, M., and Solano, F. (1992). Coelenterazine is a superoxide anion-sensitive chemiluminescent probe its usefulness in the assay of respiratory burst in neutrophils. Anal. Biochem. 206 273-277. 

Polymorphonuclear leucocytes (PMNs) employ a system comprising myeloperoxidase, hydrogen peroxide, and a halide factor to kill microorganisms and tumour cells. This process is sometimes loosely called the respiratory burst , which refers to the sudden rise in oxygen consumption by the phagocytosing neutrophils that is independent of the mitochondrial electron transport chain. 

Chronic granulomatous disease is a rare inherited disorder characterized by the failure of neutrophils, eosinophils, monocytes and macrophages to produce the respiratory burst (Curnutte and Babior, 1987) this leads to recurrent bacterial and fungal infections often starting within the first year of life. 

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