Increased expression of TRAIL receptor 3 on eosinophils in Churg-Strauss syndrome.

Abstract

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.

CONCLUSION:

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.

• Authors: Hideo Mitsuyama, Wataru Matsuyama, Masaki Watanabe, Yuko Shirahama, Ikkou Higashimoto, Takashi Wada, Mitsuhiro Osame, Kimiyoshi Arimura
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 56 Issue 2 Pg. 662-73 (Feb 2007) ISSN: 0004-3591 [Print] United States
• PMID: 17265502 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• GPI-Linked Proteins
• Receptors, Tumor Necrosis Factor, Member 10c
• TNFRSF10C protein, human
• Tumor Necrosis Factor Decoy Receptors
• Caspase 3

Topics

• Adult
• Aged
• Apoptosis (physiology)
• Asthma (genetics, metabolism, pathology)
• Caspase 3 (metabolism)
• Churg-Strauss Syndrome (etiology, metabolism, pathology)
• Eosinophils (metabolism, pathology)
• Female
• GPI-Linked Proteins
• Gene Expression Regulation
• Humans
• Lymphocytes (metabolism, pathology)
• Male
• Middle Aged
• Receptors, Tumor Necrosis Factor, Member 10c
• Tumor Necrosis Factor Decoy Receptors (metabolism)