Peroxiredoxin II expression and its association with oxidative stress and cell proliferation in human idiopathic pulmonary fibrosis.
Oxidant burden has been suggested to be a contributor to the pathogenesis of idiopathic pulmonary fibrosis (IPF). The study focused on peroxiredoxin (Prx) II, an antioxidant that has been associated with platelet-derived growth factor (PDGF) signaling and consequent cell proliferation. Localization and expression of Prx II, PDGF receptors (PDGFRalpha, PDGFRbeta), Ki67, and nitrotyrosine were assessed in control (n=10) and IPF/usual interstitial pneumonia (UIP) (n=10) lung biopsies by immunohistochemistry and morphometry. Prx II oxidation was determined by standard and non-reducing Western blots, two-dimensional gel electrophoresis, and mass spectrometry. Prx II localized in the IPF/UIP epithelium and alveolar macrophages. Prx II-positive area in the fibroblastic foci (FF) was smaller than in other parenchymal areas (p=0.03) or in the hyperplastic epithelium (p=0.01). There was no major Prx II oxidation in IPF/UIP compared with the normal lung. The FF showed only minor immunoreactivity to the PDGFRs; Ki67, a marker of cell proliferation; and nitrotyrosine, a marker of oxidative/nitrosative stress. The results suggest that Prx II oxidation does not relate to the pathogenesis of IPF/UIP and that Prx II, PDGFRs, and proliferating cells colocalize in the IPF/UIP lung. Unexpectedly, FF represented areas of low cell proliferation.
Vuorinen
Kirsi
K
Pulmonary Division, Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Ohlmeier
Steffen
S
Leppäranta
Outi
O
Salmenkivi
Kaisa
K
Myllärniemi
Marjukka
M
Kinnula
Vuokko L
VL
D015153:Blotting, Western; D049109:Cell Proliferation; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000096:biosynthesis*; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D019394:Ki-67 Antigen; C002744:3-nitrotyrosine; D014443:Tyrosine; D054464:Peroxiredoxins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta