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- W2000602719 abstract "Apoptosis is the main mechanism that regulates cell lifespan and the elimination of damaged or infected nucleatedcells. Although platelets are enucleate cells, they express atleast part of the apoptotic machinery known from nucleatedcells. In addition, they have been observed to undergoapoptotic-like events. This has been demonstrated by theactivation and translocation of Bcl-2 family members,cytochrome c release, activation of caspase-9 and ofcaspase-3 [1–10]. These observations indicate that plateletscontain the essential components needed to undergoprogrammed cell death executed in the cytoplasm. Recent-ly, in a murine model of ITP, it has been shown thatapoptotic-like processes can be induced by anti-plateletantibodies: injection of anti-GPIIb antibodies causedapoptotic-like events as well as profound thrombocytopenia[7, 11–14].In this murine ITP model, IVIg treatment wasable to decrease the apoptotic-like events and to improvethe low platelet count [7, 11–13].As no such study has been performed in paediatric ITPso far, we started to investigate whether in children withprimary ITP, an enhanced expression of markers ofapoptotic processes can be found. Furthermore, we areinterested to see if such markers correlate to platelet countand most important to clinical symptoms and if theydecrease after IVIg treatment.So far, we have shown in a limited number of patientsthat caspase-3 is activated in 40% of the platelets in patientswith primary ITP and decreases to 10% after IVIg treatment([15], manuscript in preparation). In parallel to caspase-3activation also bleeding signs decreased after IVIg therapy.In ongoing studies, we investigate caspase-3, caspase-9,caspase-8, PS-exposure and mitochondrial membrane po-tential by flow cytometry and caspases by Western blot. Wefurther will develop an immuno-fluorescence microscopyprotocol for the detection and quantification of activatedcaspases in bone marrow smears. Investigating and com-paring levels of activated caspases and other signs ofapoptosis in platelets and bone marrow samples isimportant to understand the initiation of apoptotic pro-cesses in platelets, whether apoptosis is already triggered inbone marrow or only in platelets in ITP patients. Further-more, it is important to understand whether apoptosismight contribute to the destruction of platelets in ITPpatients.To increase patient numbers, we invite other clinicians orlaboratories treating respectively investigating ITP tocollaborate with us." @default.
- W2000602719 created "2016-06-24" @default.
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- W2000602719 date "2010-04-22" @default.
- W2000602719 modified "2023-10-14" @default.
- W2000602719 title "Investigating caspases and other markers of apoptosis in ITP" @default.
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- W2000602719 doi "https://doi.org/10.1007/s00277-009-0886-4" @default.
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