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Desialylation is associated with apoptosis and phagocytosis of platelets in patients with prolonged isolated thrombocytopenia after allo-HSCT
Zhang, Xiao-Hui; Wang, Qian-Ming; Zhang, Jia-Min; Feng, Fei-Er; Wang, Feng-Rong; Chen, Huan; Zhang, Yuan-Yuan; Chen, Yu-Hong; Han, Wei; Xu, Lan-Ping; Liu, Kai-Yan; Huang, Xiao-Jun
刊名JOURNAL OF HEMATOLOGY & ONCOLOGY
2015-10-23
DOI10.1186/s13045-015-0216-3
8
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology ; Hematology
研究领域[WOS]Oncology ; Hematology
关键词[WOS]STEM-CELL TRANSPLANTATION ; GLYCOPROTEIN-IB-ALPHA ; BONE-MARROW-TRANSPLANTATION ; CHILLED BLOOD-PLATELETS ; VERSUS-HOST-DISEASE ; IMMUNE THROMBOCYTOPENIA ; CHRONIC GRAFT ; SIALIC-ACID ; IN-VITRO ; CLEARANCE
英文摘要

Background: Prolonged isolated thrombocytopenia (PT) is a frequent complication in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it is associated with an adverse prognosis. In this study, we hypothesized that desialylation on platelet surfaces was associated with PT after allo-HSCT. The mechanisms participating in this process may include NEU1 translocation, platelet apoptosis, and phagocytosis by macrophages.

Methods: PT was defined as a peripheral platelet count less than 100 x 10(9)/L without sustained anemia or leukopenia for more than 3 months after allo-HSCT. 34 patients were identified consecutively from a cohort of 255 patients who underwent allo-HSCT for hematologic malignancies between May and October 2014 at Peking University Institute of Hematology. Desialylation, enzyme expression, and phagocytosis were detected using flow cytometry, immunofluorescence, RT-PCR, Western blot, and so on.

Results: Platelets from the PT patients had significantly fewer sialic acids (P = .001) and increased beta-galactose exposure indicative of desialylation on the surface (P = .042), and serum from the PT patients showed a higher sialic acid concentration (8.400 +/- 0.2209 mu mol/L, P < .001). The sialidase NEU1 was over-expressed from mRNA to protein levels, and its catalytic activity was increased in platelets from the PT patients. Desialylation of GPIba in the PT patients was correlated with changes in 14-3-3 zeta distribution, which, relative to Bad activation, modulated the expression of Bcl-2 family proteins, depolarized the inner membrane of the mitochondria, and initiated the intrinsic mitochondria-dependent pathway of apoptosis. Macrophages derived from the THP-1 cell line preferred to phagocytize desialylated platelets from the PT patients in vitro. We also revealed that oseltamivir (400 mu mol/L) could inhibit 50 % of the sialidase activity on platelets and could protect 20 % of platelets from phagocytosis in vitro.

Conclusions: Desialylation of platelets was associated with platelet apoptosis and phagocytosis, whereas oseltamivir could reduce platelet destruction in the periphery, indicating a potential novel treatment for PT after allo-HSCT.

语种英语
WOS记录号WOS:000363288500001
项目编号2012BAI38B03 ; 81270643 ; 81470363 ; 7132194 ; 20120001110026
资助机构National Key Technology Support Program ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Specialized Research Fund for the Doctoral Program of Higher Education
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67991
专题北京大学第二临床医学院_血液科
医学人文研究院/公共教学部_哲学与社会科学系
作者单位Peking Univ, Peoples Hosp, Inst Hematol, Beijing 100044, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Xiao-Hui,Wang, Qian-Ming,Zhang, Jia-Min,et al. Desialylation is associated with apoptosis and phagocytosis of platelets in patients with prolonged isolated thrombocytopenia after allo-HSCT[J]. JOURNAL OF HEMATOLOGY &amp; ONCOLOGY,2015,8.
APA Zhang, Xiao-Hui.,Wang, Qian-Ming.,Zhang, Jia-Min.,Feng, Fei-Er.,Wang, Feng-Rong.,...&Huang, Xiao-Jun.(2015).Desialylation is associated with apoptosis and phagocytosis of platelets in patients with prolonged isolated thrombocytopenia after allo-HSCT.JOURNAL OF HEMATOLOGY & ONCOLOGY,8.
MLA Zhang, Xiao-Hui,et al."Desialylation is associated with apoptosis and phagocytosis of platelets in patients with prolonged isolated thrombocytopenia after allo-HSCT".JOURNAL OF HEMATOLOGY & ONCOLOGY 8(2015).
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