Myeloperoxidase function

Zhang R, Brennan M-L, Shen Z, MacPherson JC, Schmitt D, Molenda CE, Hazen SL. 2002a Myeloperoxidase functions as a major enzymatic catalyst for initiation of lipid peroxidation at sites of inflammation. J Biol Chem 277 46116-46122. 

M8. Marquez, L. A., Dunford, H. B., and Van Wart, H., Kinetic studies on the reaction of compound II of myeloperoxidase with ascorbic acid. Role of ascorbic acid in myeloperoxidase function. J. Biol. Chem. 265,5666-5670 (1990). 

These stimuli elicit a complex series of responses that result in cell functions such as chemotaxis and release of inflammatory compounds, oxidants, and proteases. Probably related to chemotaxis is a rapid, transient actin polymerization response. Inflammation results in part from the release of proteases and myeloperoxidase normally stored in granules inside the cell (5) and from oxidants produced by an NADPH-oxidase system (6) located primarily... 

Klebanoff SJ. Myeloperoxidase occurence and biological function. In Everse J, Everse KE, Grisham MB, eds. Peroxidases in Chemistry and Biology. Boca Raton, FL CRC Press 1991. 

Histochemical studies of bone marrow samples show that peroxidase-containing granules are detectable in promyelocytes. The human promyelo-cytic leukaemia cell line HL-60 grows easily in culture, and the cells resemble promyelocytes both structurally and functionally. Furthermore, they can be induced to differentiate in vitro upon addition of various agents, such as retinoic acid and phorbol esters, and these differentiated cells resemble more mature forms of neutrophils. HL-60 cells possess almost the same amount of myeloperoxidase (4.4 fig per 106 cells) as mature neutrophils, and the enzyme purified from these cells has the same subunit structure. The cells thus actively synthesise the enzyme only until they are induced to differentiate. This cell line has been extensively used to study the molecular events controlling the expression of enzymes such as myeloperoxidase, and also to investigate the molecular controls that lead to a cessation of their expression. 

In order to function efficiently, myeloperoxidase must be translocated from its intracellular location, the azurophilic granule, to the site of NADPH oxi-... 

Myeloperoxidase is an extremely potent, antimicrobial protein that is present in neutrophils at up to 5% of the total cell protein. Its role in the killing of a wide range of bacteria, fungi, viruses, protozoa and mammalian cells (e.g. tumour cells) is well established from in vitro studies. It also plays an important role in the inactivation of toxins and the activation of latent proteases, as well as in other functions described in section 5.4.1. In view of this apparent central role in neutrophil function during host defence, one would think that any deficiencies in this enzyme would have disastrous consequences on the ability of the host to combat infections. Until the early 1980s, this key role for myeloperoxidase in host protection seemed substantiated by the extremely low incidence of reports of patients with deficiencies of this enzyme. Indeed, up to this time, only 15 cases from 12 families had been reported worldwide. Sometimes these patients were asymptomatic but often suffered Candida infections, particularly if their myeloperoxidase deficiency was also associated with diabetes mellitus. 

It was also discovered that myeloperoxidase is not present in the neutrophils of chickens, but this deficiency is not normally associated with an increased prevalence of infections. Thus, if many healthy individuals (or chicken neutrophils) possess low or zero levels of myeloperoxidase but have no increased risk of infection, what really is the importance of the myeloperoxidase system in neutrophil function during host protection ... 

There is some evidence suggesting that camosine can upregulate immune function. Camosine s ability to react with hypochlorite anions (Formazyuk et al, 1992 Quinn et al, 1992) generated in activated leukocytes via the myeloperoxidase reaction, suggests that the dipeptide may limit hypochlori te-med ia ted oxidation in vivo (Pattison and Davies, 2006)... 

Cigarette smoke decreases the < i-PI activity in rat lung and produces a functional deficiency of protease inhibitors in the lower respiratory tract of humans (11,12). It is quite reasonable to assume that this is due to the oxidation of the essential methionine residue in i-PI. Thus, chemical modification of ax-PI by oxidation of a methionine residue to a methionine sulfoxide residue by some component of cigarette smoke or by myeloperoxidase which is released by cigarette smoke, results in inactivation of this essential protease inhibitor. The resulting imbalance of proteases and protease inhibitors in the lung then results in the development of emphysema. 

Kimura S, Ikeda-Saito M (1988) Human myeloperoxidase and thyroid peroxidase, two enzymes with separate and distinct physiological functions, are evolutionarily related members of the same gene family. Proteins 3 113-120... 

K15. Klebanoff, S. J., Myeloperoxidase-mediated antimicrobial systems and their role in leukocytic function. (J. Schultz, Ed.), In Biochemistry of Phagocytic Process, pp. 89—110. North Holland, Amsterdam, 1970. 

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