Increased expression of TRAIL receptor 3 on eosinophils in Churg-Strauss syndrome.
OBJECTIVE
Prolonged survival of eosinophils plays an important role in the pathogenesis of Churg-Strauss syndrome (CSS); however, its detailed molecular mechanism is still unclear. TRAIL and its receptors are expressed on a variety of cells, including eosinophils. In this study, we examined the expression of TRAIL receptors on eosinophils from patients with CSS.


METHODS
TRAIL receptor expression was assessed on eosinophils from healthy volunteers, patients with CSS, patients with asthma, and patients with hypereosinophilia due to parasitic infection. TRAIL-induced apoptosis of eosinophils was compared between the patients with CSS and patients with asthma. RNA interference was used to assess the effects of suppression of TRAIL receptor 3.


RESULTS
Expression of TRAIL receptor 3, a decoy receptor that acts as an antiapoptotic receptor, on eosinophils from patients with CSS was significantly higher than that in the other subjects. Moreover, in CSS, serum TRAIL receptor 3 levels showed a significant positive correlation with peripheral eosinophil counts, tissue-infiltrating eosinophils stained positive for this receptor, and peripheral T cells expressed TRAIL on their surface. Compared with asthma patients, eosinophils from CSS patients showed a significantly lower percentage of recombinant TRAIL, less autologous T cell-induced apoptosis, and decreased level of active caspase 3. Suppression of TRAIL receptor 3 through RNA interference significantly increased the recombinant TRAIL-induced apoptosis of eosinophils from CSS patients.


CONCLUSIONS
Increased expression of TRAIL receptor 3 on eosinophils from patients with CSS was observed. These alterations in TRAIL receptor 3 expression might be involved in the molecular pathogenesis of CSS eosinophilia.
Mitsuyama
Hideo
H
Kagoshima University Hospital, Kagoshima, Japan.
Matsuyama
Wataru
W
Watanabe
Masaki
M
Shirahama
Yuko
Y
Higashimoto
Ikkou
I
Wada
Takashi
T
Osame
Mitsuhiro
M
Arimura
Kimiyoshi
K
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001249:Asthma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D015267:Churg-Strauss Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004804:Eosinophils / Q000378:metabolism* / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053319:Tumor Necrosis Factor Decoy Receptors / Q000378:metabolism
D058851:GPI-Linked Proteins; D053320:Receptors, Tumor Necrosis Factor, Member 10c; C108661:TNFRSF10C protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D053148:Caspase 3