成对免疫球蛋白样受体B调控血小板活化

发布时间：2018-01-01 19:36

  本文关键词：成对免疫球蛋白样受体B调控血小板活化　出处：《上海交通大学》2015年博士论文　论文类型：学位论文

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【摘要】：小鼠成对免疫球蛋白样受体B (PIRB)和它的同源受体人类白细胞免疫球蛋白样受体B2 (LILRB2)在机体免疫、神经元轴突再生和造血干细胞分化过程中扮演着极为重要的角色,但在血小板上的表达和功能尚无研究报道。经研究,我们发现PIRB(?)LILRB2分别在小鼠和人的血小板中高表达。PIRB胞内段缺失的小鼠(PIRB-TM)患有血小板增多症,并且骨髓中巨核细胞明显增多。对血小板功能进行分析发现：与WT血小板相比,PIRB-TM血小板对激活剂引起的血小板聚集反应性明显增强,在固化纤维蛋白原上的铺展和栓块收缩更快。对下游信号通路进行分析发现：PIRB和磷酸酶Shp1/2结合；在胶原相关肽(CRP)刺激下或铺展情况下,与WT血小板相比,PIRB-TM血小板中Shp1/2的磷酸化水平明显降低；相对应地,在CRP刺激下,PIRB-TM血小板中LAT、SLP76和PLCy2的磷酸化水平明显增加,而在铺展情况下,PIRB-TM血小板中FAK第397位酪氨酸和整合素p3第759位酪氨酸的磷酸化水平也明显增加。进一步分析发现,PIRB/LILRB2的配体血管生成素样蛋白2(Angptl2)在血小板中高表达并且储存在α颗粒中。Angpt12蛋白抑制激活剂引起的血小板聚集反应和血小板在固化纤维蛋白原上的铺展。本研究首次揭示了受体PIRB和它的配体通过抑制胶原受体GPVI和整合素aⅡbβ3介导的信号,因而具有抗血栓形成的功能。
[Abstract]:Mouse immunoglobulin-like receptor B (PIRB) and its homologous receptor human leukocyte immunoglobulin-like receptor B 2 (LILRB2) were immunized in vivo. Neuronal axonal regeneration and hematopoietic stem cell differentiation play a very important role, but the expression and function on platelets have not been reported. LILRB2 was highly expressed in mouse and human platelets. PIRB-TM2 with deletion of intracellular segment of PIRB was found to have thrombocytopenia. Compared with WT platelets, PIRB-TM platelets were more responsive to platelet aggregation induced by activator. The spreading on the fibrinogen solidified and the blockage contracting were faster. The downstream signal pathway was found to bind to the Shp1/2 of PIRB and phosphatase. The phosphorylation level of Shp1/2 in PIRB-TM platelets was significantly lower than that in WT platelets stimulated or spread by collagen related peptide CRP. In contrast, the phosphorylation levels of LATA SLP76 and PLCy2 in PIRB-TM platelets stimulated by CRP were significantly increased, but the phosphorylation levels of LATA SLP76 and PLCy2 in PIRB-TM platelets were significantly increased under the condition of spreading. The phosphorylation levels of tyrosine at position 397 of FAK and of integrin p3 at position 759 in PIRB-TM platelets were also significantly increased. PIRB/LILRB2 ligand angiopoietin like protein 2Angptl2). Platelet aggregation response induced by high expression in platelets and stored in 伪 particles. Angpt12 protein activator and platelets spreading on fibrinogen solidified. This study first revealed the receptor P. IRB and its ligand inhibit the signal mediated by collagen receptor GPVI and integrin a 鈪，

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