Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents

¹ Dept of Respiratory Medicine, University Hospital Maastricht, Maastricht, The Netherlands
² Dept of Pathology and Laboratory Medicine, University Medical Center Groningen, Groningen, The Netherlands
³ Dept of Pathology, University of Vermont, Burlington, VT 05405 USA

^* To whom correspondence should be addressed. E-mail: j.vernooy{at}pul.unimaas.nl.

	Abstract

During extensive inflammation, neutrophils undergo secondary necrosis causing myeloperoxidase (MPO) release which may damage resident lung cells. Recent observations suggest that MPO has pro-inflammatory properties, independent of its enzymatic activityHoHHHimportant role in thas. The aims of this study were to characterize MPO internalization by lung epithelial cells and to investigate the effect of MPO on oxidative stress, DNA damage and cytokine production by lung epithelial cells.

Human alveolar and bronchial epithelial cells were stimulated with MPO with or without priming the cells with pro-inflammatory stimuli. MPO protein was detected in cell cytoplasm. Expression of heme-oxygenase (HO)-1 and DNA strand breakage were determined. The production of interleukin (IL)-8 and 6 were measured.

Analyses of MPO stimulated cells demonstrated MPO presence in the cells. HO-1 expression was increased after MPO stimulation and increased further when cells were primed before MPO stimulation. MPO exposure also induced DNA strand breakage. Interestingly, MPO inhibited IL-8 production in bronchial, but not alveolar epithelium.

In conclusion, alveolar and bronchial epithelial cells can internalize MPO. Stimulation with MPO increases HO-1 expression and DNA strand breakage, suggesting cell damaging capacity of MPO. In addition, MPO inhibited IL-8 production by bronchial epithelial cells, indicating a negative feedback loop for neutrophil recruitment.

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