Of mice and men:: Comparison of the ultrastructure of megakaryocytes and platelets
Of mice and men:: Comparison of the ultrastructure of megakaryocytes and platelets
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DOI：
10.1016/s0301-472x(01)00733-0
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发表时间：
2001-11-01
影响因子：
2.6
通讯作者：
Cramer, EM
中科院分区：
文献类型：
--
作者：
Schmitt, A;Guichard, J;Cramer, EM
目标。小鼠为体内研究血小板和巨核细胞生物学提供了一个很好的模型。鉴于转基因和基因敲除小鼠的使用越来越多，很重要的一点是，明确界定小鼠和人类血小板/Mk生物学之间的任何异同。因此，本研究的目的是详细比较和对比巨噬细胞集落刺激因子、血小板之间的任何显著的形态差异，以及人类和小鼠的血栓形成机制。本文综述了小鼠、人血小板和巨噬细胞集落刺激因子的独特结构和超微结构特征。通过使用针对人血小板蛋白的多克隆抗体，免疫电子显微镜也在小鼠细胞中定位了几种血小板和Mk糖蛋白，并与现有的人类数据进行了比较。最后，对成熟的小鼠和人MKs在培养和骨髓中的超微结构进行了详细的观察，以便于比较体内和体外的血小板生成。人类和小鼠的血小板在形态上存在着显著的差异。小鼠的血小板比人类的更小、更多，并且表现出更大的颗粒异质性。免疫电子显微镜还显示，小鼠的血小板高度区域化。事实上，它们与人类α颗粒非常相似，具有不对称的von Willebrand因子(VWF)分布，并在颗粒限制膜上标记α(IIb)β(3)和P-选择素(CD62p)。在活体中，小鼠而不是人的MKs也一致地定位于脾内。首次报道了伴随着小鼠MKS的血小板形成和释放的亚细胞事件，并与人类进行了比较。在血小板形成前的分界膜重分布途径上发现了一致的差异，这可能对阐明血小板释放的机制有重要意义。人和小鼠血小板及巨噬细胞集落刺激因子在超微结构上表现出几个特征差异(大小、数量、组织分布、血小板脱落)，这些在本报告中得到了强调和分析。然而，由于它们也有许多相似之处(细胞器和糖蛋白的亚细胞分布)，小鼠提供了一个很好的体内模型来研究人类Mk和血小板生物学的各个方面。(C)2001年国际实验血液学学会。爱思唯尔科学公司出版。
Objective. Mice provide an excellent model for studying platelet and megakaryocyte (Mk) biology in vivo. Given the increasing use of transgenic and knockout mice, it is important that any similarities and differences between murine and human platelet/Mk biology be well defined. Therefore the objective of this study was to compare and contrast in detail any significant morphological differences between Mks, platelets, and mechanisms of thrombopoiesis in humans and mice.Methods. The distinctive structural and ultrastructural features of murine and human platelets and Mks are reviewed. Several platelet and Mk glycoproteins were also localized in murine cells by immunoelectron microscopy using polyclonal antibodies directed against human platelet proteins and compared to existing human data. Finally, the ultrastructure of maturing murine and human Mks in culture and bone marrow were examined in detail to facilitate a comparison of either in vivo or in vitro platelet production.Results. Human and murine platelets exhibit significant but well-established morphological differences. Murine platelets are smaller and more numerous and display much greater granule heterogeneity than their human counterparts. Immunoelectron microscopy also demonstrated that murine platelet alpha -gramiles, are highly compartmentalized. In fact, they are remarkably similar to human alpha -granules, with asymmetrical distribution of von Willebrand factor (vWF), and labeling of alpha (IIb)beta (3) and P-selectin (CD62P) in the granule limiting membrane. In vivo, murine but not human Mks are also consistently localized within the, spleen. Subcellular events accompanying platelet formation and release by murine Mks are presented for the first time, and compared to human. Consistent differences were found in the pathway of redistribution of demarcation membranes preceding platelet formation, which may be important for the clarification of the mechanism of platelet release.Conclusion. Human and murine platelets and Mks display several characteristic ultrastructural differences (size, number, histological distribution, platelet shedding) which have been emphasized and analyzed in this report. Nevertheless, since there are also many close similarities (organelle and glycoprotein subcellular distribution) mice offer an excellent in vivo model to study various aspects of human Mk and platelet biology. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.