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伯克利镰状细胞小鼠的血小板形态和功能异常

Morphological and functional platelet abnormalities in Berkeley sickle cell mice.

作者信息

Shet Arun S, Hoffmann Thomas J, Jirouskova Marketa, Janczak Christin A, Stevens Jacqueline R M, Adamson Adewole, Mohandas Narla, Manci Elizabeth A, Cynober Therese, Coller Barry S

机构信息

The Laboratory of Blood and Vascular Biology, Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.

出版信息

Blood Cells Mol Dis. 2008 Jul-Aug;41(1):109-18. doi: 10.1016/j.bcmd.2008.01.008. Epub 2008 Apr 18.

Abstract

Berkeley sickle cell mice are used as animal models of human sickle cell disease but there are no reports of platelet studies in this model. Since humans with sickle cell disease have platelet abnormalities, we studied platelet morphology and function in Berkeley mice (SS). We observed elevated mean platelet forward angle light scatter (FSC) values (an indirect measure of platelet volume) in SS compared to wild type (WT) (37+/-3.2 vs. 27+/-1.4, mean+/-SD; p<0.001), in association with moderate thrombocytopenia (505+/-49 x 10(3)/microl vs. 1151+/-162 x 10(3)/microl; p<0.001). Despite having marked splenomegaly, SS mice had elevated levels of Howell-Jolly bodies and "pocked" erythrocytes (p<0.001 for both) suggesting splenic dysfunction. SS mice also had elevated numbers of thiazole orange positive platelets (5+/-1% vs. 1+/-1%; p<0.001), normal to low plasma thrombopoietin levels, normal plasma glycocalicin levels, normal levels of platelet recovery, and near normal platelet life spans. Platelets from SS mice bound more fibrinogen and antibody to P-selectin following activation with a threshold concentration of a protease activated receptor (PAR)-4 peptide compared to WT mice. Enlarged platelets are associated with a predisposition to arterial thrombosis in humans and some humans with SCD have been reported to have large platelets. Thus, additional studies are needed to assess whether large platelets contribute either to pulmonary hypertension or the large vessel arterial occlusion that produces stroke in some children with sickle cell disease.

摘要

伯克利镰状细胞小鼠被用作人类镰状细胞病的动物模型,但尚无关于该模型中血小板研究的报道。由于患有镰状细胞病的人类存在血小板异常,我们研究了伯克利小鼠(SS)的血小板形态和功能。我们观察到,与野生型(WT)相比,SS小鼠的平均血小板前向角光散射(FSC)值升高(血小板体积的间接测量指标)(37±3.2对27±1.4,平均值±标准差;p<0.001),同时伴有中度血小板减少(505±49×10³/微升对1151±162×10³/微升;p<0.001)。尽管SS小鼠有明显的脾肿大,但其豪-焦小体和“有凹痕”红细胞水平升高(两者p<0.001),提示脾功能障碍。SS小鼠噻唑橙阳性血小板数量也增加(5±1%对1±1%;p<0.001),血浆血小板生成素水平正常至偏低,血浆糖萼蛋白水平正常,血小板恢复水平正常,血小板寿命接近正常。与WT小鼠相比,用蛋白酶激活受体(PAR)-4肽的阈值浓度激活后,SS小鼠的血小板结合更多纤维蛋白原和抗P-选择素抗体。在人类中,增大的血小板与动脉血栓形成倾向有关,据报道一些患有镰状细胞病的人有大血小板。因此,需要进一步研究来评估大血小板是否会导致肺动脉高压或导致一些镰状细胞病儿童中风的大血管动脉闭塞。

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