Human myeloperoxidase in innate and acquired immunity

Arnhold, J; Flemmig, Jörg

doi:10.1016/j.abb.2010.04.008

Cited by 221 publications

(189 citation statements)

References 314 publications

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“…38,48 Inflammatory sites, as the result of microorganism infections or injured tissues, are characterized by increased levels of MPO. Indeed, studies have increasingly suggested potential links between MPO and the development of diverse diseases.…”

Section: Discussionmentioning

confidence: 99%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

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Rotenone exposure has emerged as an environmental risk factor for inflammation-associated neurodegenerative diseases. However, the underlying mechanisms responsible for the harmful effects of rotenone in the brain remain poorly understood. Herein, we report that myeloperoxidase (MPO) may have a potential regulatory role in rotenone-exposed brain-resident immune cells. We show that microglia, unlike neurons, do not undergo death; instead, they exhibit distinctive activated properties under rotenone-exposed conditions. Once activated by rotenone, microglia show increased production of reactive oxygen species, particularly HOCl. Notably, MPO, an HOClproducing enzyme that is undetectable under normal conditions, is significantly increased after exposure to rotenone. MPO-exposed glial cells also display characteristics of activated cells, producing proinflammatory cytokines and increasing their phagocytic activity. Interestingly, our studies with MPO inhibitors and MPO-knockout mice reveal that MPO deficiency potentiates, rather than inhibits, the rotenone-induced activated state of glia and promotes glial cell death. Furthermore, rotenone-triggered neuronal injury was more apparent in co-cultures with glial cells from Mpo ؊/؊ mice than in those from wildtype mice. Collectively, our data provide evidence that MPO has dual functionality under rotenone-exposed conditions, playing a critical regulatory role in modulating pathological and protective events in the brain.

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Section: Discussionmentioning

confidence: 99%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

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“…MPO, which is expressed in activated astrocytes, is the key enzyme involved in the generation of cytotoxic ROS/RNS (57,58). These astroglial MPO-derived oxidants can be released and subsequently exert toxic effects on adjacent mesencephalic DA neurons in the MPTP model (15).…”

Section: Discussionmentioning

confidence: 99%

Ethyl Pyruvate Rescues Nigrostriatal Dopaminergic Neurons by Regulating Glial Activation in a Mouse Model of Parkinson’s Disease

Huh

Chung

Piao

et al. 2011

The Journal of Immunology

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This study examined whether ethyl pyruvate (EP) promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage Ag complex-1, and/or glial fibrillary acidic protein immunoreactivity. Western blotting and immunohistochemistry showed activation of microglial NADPH oxidase and astroglial myeloperoxidase (MPO) and subsequent reactive oxygen species/reactive nitrogen species production and oxidative DNA damage in the MPTP-treated substantia nigra. Treatment with EP prevented degeneration of nigrostriatal DA neurons, increased striatal dopamine levels, and improved motor function. This neuroprotection afforded by EP was associated with the suppression of astroglial MPO expression, NADPH oxidase-, and/or inducible NO synthase-derived reactive oxygen species/reactive nitrogen species production by activated microglia. Interestingly, EP was found to protect DA neurons from 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia but not in neuron-enriched mesencephalic cultures devoid of microglia. The present findings show that EP may inhibit glial-mediated oxidative stress, suggesting that EP may have therapeutic value in the treatment of aspects of Parkinson’s disease related to glia-derived oxidative damage.

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“…Under physiological relevant conditions, the production of hypochlorous acid (HOCl) and hypothiocyanite ( -OSCN) is important (van Dalen et al, 1997). As myeloperoxidase is strongly expressed in PMNs (and to a lesser extent in monocytes) there is a great interest to understand specific functions of this enzyme during immune reactions of PMNs (Arnhold & Flemmig, 2010).…”

Section: Generation Of Oxidants During Pmn Apoptosismentioning

confidence: 99%