Myeloperoxidase Deficiency

Nauseef, William M.

doi:10.1016/s0889-8588(18)30634-8

Cited by 101 publications

(70 citation statements)

References 192 publications

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“…Myeloperoxidase expression has previously only been described in neutrophils (Nauseef 1988), monocytes (Nauseef 1988), and certain populations of tissue macrophages (Daugherty et al 1994;Nagra et al 1997;Sugiyama et al 2001). The enzyme plays a critical role in generating oxidizing intermediates during phagocytosis of invading pathogens (Klebanoff and Clark 1978;Hurst and Barrette 1989;Gaut et al 2001) and contributes to tissue damage during atherogenesis and other chronic inflammatory diseases (Heinecke 1999).…”

Section: Discussionsupporting

confidence: 86%

“…Cultured neuronal cell types contain myeloperoxidase immunoreactivity and mRNA Neuronal myeloperoxidase immunoreactivity was a surprising finding as only myeloid-derived cells have been reported to contain myeloperoxidase (Nauseef 1988). To confirm neuronal expression of the enzyme, we used cultured rat primary hippocampal and neocortical neurons, greater than 99% neurons by MAP-2 staining, as well as a transformed neuronal cell line, HT-22, derived from the mouse hippocampus, to look for myeloperoxidase by immunoblot and mRNA.…”

Section: Resultsmentioning

confidence: 99%

“…Myeloperoxidase is a heme protein expressed in professional phagocytic cells such as neutrophils (Nauseef 1988), monocytes (Nauseef 1988), and certain populations of tissue macrophages (Daugherty et al 1994;Nagra et al 1997), including microglia (Reynolds et al 1999). The best characterized role of myeloperoxidase is in host defense (Klebanoff and Clark 1978;Hurst and Barrette 1989;Gaut et al 2001) where the enzyme converts hydrogen peroxide generated from the oxidative burst to the potent microbicidal oxidant hypochlorous acid (HOCl; Harrison and Schultz 1976).…”

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confidence: 99%

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Neuronal expression of myeloperoxidase is increased in Alzheimer's disease

Green

Mendez

Jacob

et al. 2004

Journal of Neurochemistry

291

196

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Myeloperoxidase, a heme protein expressed by professional phagocytic cells, generates an array of oxidants which are proposed to contribute to tissue damage during inflammation. We now report that enzymatically active myeloperoxidase and its characteristic amino acid oxidation products are present in human brain. Further, expression of myeloperoxidase is increased in brain tissue showing Alzheimer's neuropathology. Consistent with expression in phagocytic cells, myeloperoxidase immunoreactivity was present in some activated microglia in Alzheimer brains. However, the majority of immunoreactive material in brain localized with amyloid plaques and, surprisingly, neurons including granule and pyramidal neurons of the hippocampus. Confirming neuronal localization of the enzyme, several neuronal cell lines as well as primary neuronal cultures expressed myeloperoxidase protein. Myeloperoxidase mRNA was also detected in neuronal cell lines. These results reveal the unexpected presence of myeloperoxidase in neurons. The increase in neuronal myeloperoxidase expression we observed in Alzheimer disease brains raises the possibility that the enzyme contributes to the oxidative stress implicated in the pathogenesis of the neurodegenerative disorder.

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Section: Discussionsupporting

confidence: 86%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Neuronal expression of myeloperoxidase is increased in Alzheimer's disease

Green

Mendez

Jacob

et al. 2004

Journal of Neurochemistry

291

196

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“…1 an automatic blood cell counter, the Bayer/Technicon H3. The introduction of such systems in routine blood cell analysis contributed mainly to the detection of partial or complete myeloperoxidase deficiency, which is a rather frequent event (prevalence of 1 :2000-1 :4000) (3). Considering the important role of HOC1 for effective killing of microorganisms, it is surprising that most myeloperoxidase deficient persons do not suffer from life threatening infections more frequently than persons with normal myeloperoxidase activity.…”

Section: Introductionmentioning

confidence: 99%

Phagocytic Activity and Oxidative Burst of Granulocytes in Persons with Myeloperoxidase Deficiency

Gerber¹,

Kuçi²,

Zipfel³

et al. 1996

CCLM

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Summary:In the present study, phagocytosis and the oxidative metabolism of neutrophil granulocytes from five clinically healthy persons with different degrees of myeloperoxidase deficiency were investigated and compared to those of normal persons. The identification of individuals with myeloperoxidase deficiency was performed with the Bayer/Technicon H3 blood cell counter, which differentiates the leukocytes by measuring the peroxidase activity. Neutrophils of three out of five investigated myeloperoxidase deficient persons showed extremly low peroxidase indices (-53 and lower), but only the neutrophils of one person totally lacked myeloperoxidase. This was demonstrated by comparing myeloperoxidase mass concentration measured with an enzyme immunoassay, lack of HOC1 production, and was further confirmed by measuring luminol-and lucigenin-enhanced chemiluminescence. Characteristically, myeloperoxidase deficient granulocytes showed a strikingly decreased luminol-enhanced chemiluminescence while the lucigenin-enhanced chemiluminescence was significantly increased compared to normal granulocytes. Although there is a DNA sequence homology of about 70%, the activity of peroxidase in eosinophils was not affected in any myeloperoxidase deficient person investigated. Moreover, a person with a very rare defect of eosinophil peroxidase had completely normal myeloperoxidase activity. The lack of myeloperoxidase activity is compensated for by an increased phagocytic activity, an increased production of Superoxide anion (lucigeninchemiluminescence) and probably by an alternative metabolism of H 2 O 2 ; since persons lacking myeloperoxidase activity do not normally suffer from severe infections, H 2 O 2 is obviously metabolized to other reactive oxygen substrates than HOC1, e. g. to OH-radicals.

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“…Moreover, phagocytes, which congregate at sites of inflammation, might be an important source of oxidants that create such damage. One pathway involves myeloperoxidase (MPO), a heme protein released by phagocytes (12)(13)(14). MPO uses H 2 O 2 and chloride to generate the powerful oxidant hypochlorous acid (HOCl):…”

mentioning

confidence: 99%

The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport

Bergt

Pennathur

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

405

375

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Although oxidatively damaged lipoproteins are implicated in vascular injury, there is little information regarding the role of highdensity lipoprotein (HDL) oxidation in atherogenesis. One potential pathway involves hypochlorous acid (HOCl) produced by myeloperoxidase (MPO), a heme protein secreted by phagocytes. We previously showed that 3-chlorotyrosine is a specific product of HOCl. Therefore, to explore the role of oxidized HDL in the pathogenesis of vascular disease, we used MS to quantify 3-chlorotyrosine in HDL isolated from plasma and atherosclerotic tissue. HDL from human aortic atherosclerotic intima had an 8-fold higher level of 3-chlorotyrosine than plasma HDL. Tandem MS analysis identified MPO as a component of lesion HDL, suggesting that the two interact in the artery wall. Moreover, immunohistochemical studies found that specific epitopes derived from HOCl colocalized with apolipoprotein A-I, the major protein of HDL. These observations strongly support the hypothesis that MPO promotes HDL oxidation in the human artery wall. Levels of 3-chlorotyrosine were elevated in HDL isolated from the blood of humans with established coronary artery disease, suggesting that circulating levels of oxidized HDL represent a unique marker for clinically significant atherosclerosis. HDL or lipid-free apolipoprotein A-I exposed to HOCl was less able to remove cholesterol from cultured cells by a pathway requiring the cell membrane transporter ATP-binding cassette transporter A1. The detection of 3-chlorotyrosine in HDL isolated from vascular lesions raises the possibility that MPO, by virtue of its ability to form HOCl, may promote atherogenesis by counteracting the established antiatherogenic effects of HDL and the ATP-binding cassette transporter A1 pathway.

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Myeloperoxidase Deficiency

Cited by 101 publications

References 192 publications

Neuronal expression of myeloperoxidase is increased in Alzheimer's disease

Neuronal expression of myeloperoxidase is increased in Alzheimer's disease

Phagocytic Activity and Oxidative Burst of Granulocytes in Persons with Myeloperoxidase Deficiency

The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport

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