Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents.
During extensive inflammation, neutrophils undergo secondary necrosis causing myeloperoxidase (MPO) release that may damage resident lung cells. Recent observations suggest that MPO has pro-inflammatory properties, independent of its enzymatic activity. The aims of the present study were to characterise MPO internalisation 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 the cell cytoplasm. Expression of haemoxygenase (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 internalise myeloperoxidase. Stimulation with myeloperoxidase increases haemoxygenase-1 expression and DNA strand breakage, suggesting cell damaging capacity of myeloperoxidase. In addition, myeloperoxidase inhibited interleukin-8 production by bronchial epithelial cells, indicating a negative feedback loop for neutrophil recruitment.
Haegens
A
A
Dept of Respiratory Medicine, University Hospital Maastricht, P.O. Box 5800, NL-6202 AZ Maastricht, The Netherlands.
Vernooy
J H J
JH
Heeringa
P
P
Mossman
B T
BT
Wouters
E F M
EF
D000704:Analysis of Variance; D015153:Blotting, Western; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000166:cytology; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000009:adverse effects* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011336:Probability; D011650:Pulmonary Alveoli / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012680:Sensitivity and Specificity
D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D009195:Peroxidase; D051547:Heme Oxygenase-1