Anti-Human CASP2 (p18,Cleaved-Gly170) polyclonal antibody

An imbalance between cellular apoptosis and survival may be critical for the pathogenesis of lymphoma. Therefore, the gene expression pattern in lymph node preparations from patients with mantle cell lymphoma (MCL) was compared to the pattern in nonmalignant hyperplastic lymph nodes (HLs). Oligonucleotide microarray analysis was performed comparing 5 MCLs to 4 HLs using high-density microarrays. The expression data were analyzed using Genespring software. For confirmation, the expression of selected genes was analyzed by real-time polymerase chain reaction using the RNA extracted from 16 MCL and 12 HL samples. The focus was on 42 genes that were at least 3-fold down-regulated in MCL; in addition to the B-cell leukemia 2 (BCL2) system other apoptotic pathways were altered in MCL. The FAS-assoclated via death domain (FADD) gene that acts downstream of the FAS cascade as a key gene to induce apoptosis was more than 10-fold down-regulated in MCL. Furthermore, the death-associated protein 6 (DAXX) gene, the caspase 2 (CASP2) gene, and the RIPK1 domain containing adapter with death domain (RAIDD) gene, which are key genes in other proapoptotic pathways, were also decreased in the MCL samples. The suggestion is made that in addition to the known overexpression of cyclin D1, which drives entry into the cell cycle, disturbances of pathways associated with apoptosis contribute to the development of MCL. (C) 2001 by The American Society of Hematology.

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-kappa B (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.