Intrinsic pathway of apoptosis in peripheral blood eosinophils of Churg-Strauss syndrome.
OBJECTIVE
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.
Jakiela
Bogdan
B
Department of Medicine, Jagiellonian University Medical College, ul. Skawinska 8, 31-066 Krakow, Poland.
Szczeklik
Wojciech
W
Sokolowska
Barbara
B
Mastalerz
Lucyna
L
Sanak
Marek
M
Plutecka
Hanna
H
Szczeklik
Andrzej
A
D000328:Adult; D015703:Antigens, CD / Q000097:blood; D000945:Antigens, Differentiation, T-Lymphocyte / Q000097:blood; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D015267:Churg-Strauss Syndrome / Q000097:blood* / Q000276:immunology; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015415:Biomarkers; D053645:Interleukin-2 Receptor alpha Subunit; D015848:Interleukin-5; D037181:Lectins, C-Type; D000099192:CD69 Antigens