Reduction in superoxide dismutase expression in the epithelial mucosa of eosinophilic chronic rhinosinusitis with nasal polyps.
BACKGROUND
Eosinophils generate large amounts of oxidant species. The eosinophil-dominant type of chronic rhinosinusitis (CRS) with nasal polyps is related to more extensive disease and a decreased likelihood of surgical success. Superoxide dismutase (SOD) is the first-line and only antioxidant enzyme that converts superoxide to hydrogen peroxide.


METHODS
The patients with CRS with nasal polyps were divided into eosinophilic and noneosinophilic groups. The expression of three isoforms of SOD, intracellular copper-zinc SOD (CuZnSOD), mitochondrial manganese SOD (MnSOD) and extracellular SOD (ECSOD), were examined by enzyme activity assay, immunohistochemistry and quantitative real-time RT-PCR sampled by laser capture microdissection.


RESULTS
SOD activity in the eosinophilic and noneosinophilic groups was significantly reduced compared to that of the control groups. Immunostaining of both CuZnSOD and MnSOD in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. CuZnSOD mRNA of the eosinophilic group was significantly decreased compared with that of the control group, whereas MnSOD mRNA in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. Neither immunoreactivity nor mRNA of ECSOD was different among the three groups. The degree of epithelial damage and disease severity were inversely correlated with CuZnSOD and MnSOD immunoreactivity.


CONCLUSIONS
The reduction in SOD activity and the downregulation of the SOD message are suggested to be related to eosinophil recruitment and epithelial damage of CRS with nasal polyps.
Department of Otorhinolaryngology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
N
N
Ono
T
T
Kusunoki
M
M
Miwa
M
M
Hirotsu
A
A
Shiozawa
K
K
Ikeda
D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D009092:Mucous Membrane / Q000201:enzymology / Q000276:immunology; D009298:Nasal Polyps / Q000150:complications; D012333:RNA, Messenger / Q000096:biosynthesis; D012221:Rhinitis, Allergic, Perennial / Q000150:complications / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism*; D012852:Sinusitis / Q000201:enzymology* / Q000276:immunology; D013482:Superoxide Dismutase / Q000378:metabolism*
D012333:RNA, Messenger; D013482:Superoxide Dismutase