Apoptosis in megakaryocytes: Safeguard and threat for thrombopoiesis.

Platelets, generated from precursor megakaryocytes (MKs), are central mediators of hemostasis and thrombosis. The process of thrombopoiesis is extremely complex, regulated by multiple factors, and related to many cellular events including apoptosis. However, the role of apoptosis in thrombopoiesis has been controversial for many years. Some researchers believe that apoptosis is an ally of thrombopoiesis and platelets production is apoptosis-dependent, while others have suggested that apoptosis is dispensable for thrombopoiesis, and is even inhibited during this process. In this review, we will focus on this conflict, discuss the relationship between megakaryocytopoiesis, thrombopoiesis and apoptosis. In addition, we also consider why such a vast number of studies draw opposite conclusions of the role of apoptosis in thrombopoiesis, and try to figure out the truth behind the mystery. This review provides more comprehensive insights into the relationship between megakaryocytopoiesis, thrombopoiesis, and apoptosis and finds some clues for the possible pathological mechanisms of platelet disorders caused by abnormal apoptosis.

Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation.

Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIMEL , FAS, FASL, A1, BCL2, BCLXL , CFLIPL and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIMEL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8+ Fas+ T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIPL and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLXL and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation.

Action of DcR3 recombinant protein of myocardial tissue in diabetic rats / 中国免疫学杂志

Objective:To study the expression of DcR3 of myocardial tissue in diabetic mouse and normal rats and the impact of DcR3 recombinant protein to the expression of related molecules and myocardial cell apoptosis to discuss the action of DcR3 to myocardial cell apoptosis in Diabetic rats.Methods:Intraperitoneally injected streptozotocin one time to establish the model of Diabetic rats.Injected different doses of DcR3 recombinant protein to tail vein[1.2 mg/(rat? d),0.8 mg/(rat? d),0.4 mg/(rat? d)] 40 d. The expression of DcR3 mRNA, Fas mRNA and FasL mRNA of myocardial tissue was detected with RT-PCR;the expression of apoptosis related molecules Bcl-2 and Caspase-8 was analyzed with Western blot;the IL-1β, TNF-αand LFN-γof the blood was detected with double antibody sandwich ELISA;the percentage of myocardial cell apoptosis was observed with HE dyeing.Results:To compare the DcR3 treatment group with diabetic group,the expression DcR3 of myocardial tissue was high,the expression of Fas mRNA and FasL mRNA was descended.The Caspase-8 protein was ascended and the Bcl-2 protein was descended.The middle dose group was the most obvious.the IL-1β,TNF-αand IFN-γin the blood was descended differently in each DcR3 treatment group(P<0.05,P<0.01).The percentage of myocardial cell apoptosis was declined(P<0.05).Conclusion:DcR3 recombinant protein have the action of inhibiting the rats′myocardial cell apoptosis,the mechanism is related to competing with Fas,blocking-up FasL of inducing apoptosis, expressing DcR3 of myocardial cell,the descending of apoptosis related factors Caspase-8,the ascending of Bcl-2 and the reduction of cytokine levels.