本文關(guān)鍵詞：成對(duì)免疫球蛋白樣受體B調(diào)控血小板活化　出處：《上海交通大學(xué)》2015年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： PIRB Angptl2 GPⅥ 整合素αⅡbβ3 血小板

【摘要】：小鼠成對(duì)免疫球蛋白樣受體B (PIRB)和它的同源受體人類白細(xì)胞免疫球蛋白樣受體B2 (LILRB2)在機(jī)體免疫、神經(jīng)元軸突再生和造血干細(xì)胞分化過(guò)程中扮演著極為重要的角色,但在血小板上的表達(dá)和功能尚無(wú)研究報(bào)道。經(jīng)研究,我們發(fā)現(xiàn)PIRB(?)LILRB2分別在小鼠和人的血小板中高表達(dá)。PIRB胞內(nèi)段缺失的小鼠(PIRB-TM)患有血小板增多癥,并且骨髓中巨核細(xì)胞明顯增多。對(duì)血小板功能進(jìn)行分析發(fā)現(xiàn)：與WT血小板相比,PIRB-TM血小板對(duì)激活劑引起的血小板聚集反應(yīng)性明顯增強(qiáng),在固化纖維蛋白原上的鋪展和栓塊收縮更快。對(duì)下游信號(hào)通路進(jìn)行分析發(fā)現(xiàn)：PIRB和磷酸酶Shp1/2結(jié)合；在膠原相關(guān)肽(CRP)刺激下或鋪展情況下,與WT血小板相比,PIRB-TM血小板中Shp1/2的磷酸化水平明顯降低；相對(duì)應(yīng)地,在CRP刺激下,PIRB-TM血小板中LAT、SLP76和PLCy2的磷酸化水平明顯增加,而在鋪展情況下,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顯增加。進(jìn)一步分析發(fā)現(xiàn),PIRB/LILRB2的配體血管生成素樣蛋白2(Angptl2)在血小板中高表達(dá)并且儲(chǔ)存在α顆粒中。Angpt12蛋白抑制激活劑引起的血小板聚集反應(yīng)和血小板在固化纖維蛋白原上的鋪展。本研究首次揭示了受體PIRB和它的配體通過(guò)抑制膠原受體GPVI和整合素aⅡbβ3介導(dǎo)的信號(hào),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 偽 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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