Intrinsic pathway of apoptosis in peripheral blood eosinophils of Churg–Strauss syndrome
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OBJECTIVES: Churg-Strauss syndrome (CSS) is a rare necrotizing vasculitis associated with asthma, blood and tissue eosinophilia and granuloma formation. We wondered whether eosinophil accumulation in CSS results from the defect of intrinsic apoptosis pathway in blood eosinophils, leading to their prolonged survival. METHODS: We analysed immunophenotype (flow cytometry), expression of apoptosis-related genes (real-time PCR) and spontaneous apoptosis in blood eosinophils isolated from nine patients in exacerbation (active CSS), seven patients in remission (inactive CSS) and 14 matched healthy subjects. Serum IL-5 levels were also measured. RESULTS: In active CSS, blood eosinophils were characterized by small (<2-fold) decrease in expression of a few genes, primarily proapoptotic (e.g. BCL2L13, CASP2, CARD4) or involved in regulation of NF-kappaB (IKBKB, REL), but they did not differ in the rate of spontaneous apoptosis, when compared with other groups. Only selected genes were positively (BNIPL, PYCARD, CASP8, CRADD, BCAP31), or negatively (IKBKE) correlated with disease activity. In active CSS, eosinophils expressed activation markers (CD69, CD25), especially in subjects with most severe disease and elevated serum IL-5. CONCLUSIONS: High susceptibility of peripheral blood eosinophils to spontaneous apoptosis in vitro, and minor changes in expression of apoptotic-related genes in transcriptome analysis, do not support the hypothesis on intrinsic defect in apoptosis, as the cause of eosinophil accumulation in CSS.
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