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学科主题: 临床医学
题名:
Desialylation is associated with apoptosis and phagocytosis of platelets in patients with prolonged isolated thrombocytopenia after allo-HSCT
作者: 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
发表日期: 2015-10-23
DOI: 10.1186/s13045-015-0216-3
卷: 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
所属项目编号: 2012BAI38B03 ; 81270643 ; 81470363 ; 7132194 ; 20120001110026
项目资助者: 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
WOS记录号: WOS:000363288500001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67991
Appears in Collections:北京大学第二临床医学院_血液科_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Inst Hematol, Beijing 100044, Peoples R China

Recommended Citation:
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.
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