Human Platelet Vesicles Exhibit Distinct Size and Proteome.

Human Platelet Vesicles Exhibit Distinct Size and Proteome.
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人类血小板囊泡表现出不同的大小和蛋白质组。

DOI:
10.1021/acs.jproteome.7b00309
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发表时间:
2017
影响因子:
4.4
通讯作者:
Walz,DanielA
Walz,DanielA
中科院分区:
生物学2区
文献类型:
--
作者:
Jena,BhanuP;Stemmer,PaulM;Wang,Sunxi;Mao,Guangzhao;Lewis,KennethT;Walz,DanielA

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在过去的50年里,分离的血小板在伤口愈合、癌症治疗、器官和组织移植等方面的使用受到限制。其不受限制使用的主要障碍是,除其他外,生长因子的浓度过高以及促血管生成和抗血管生成蛋白的存在。为了克服这个问题,需要分离和分离含有不同因子的膜结合分泌囊泡。在目前的研究中,使用原子力显微镜(AFM)和质谱法从人血小板分离的分泌囊泡的高分辨率成像,使其免疫分离后的剩余囊泡的大小和组成的表征。渗透裂解后获得的剩余囊泡,当进行免疫分离时,采用不同的囊泡相关膜蛋白(VAMP)的抗体,第一次证明,VAMP-3-,VAMP-7-,和VAMP-8-特异性囊泡各自具有不同的大小范围和组成。这些结果提供了一个窗口到我们的理解的异质人口的囊泡在人类血小板和它们的稳定性后,使用AFM和渗透裂解的血小板物理操作。这项研究进一步提供了一个平台,分离和血小板颗粒的详细表征,为他们未来的治疗用途的承诺。此外,研究结果表明,细胞中发现的不同大小的分泌囊泡反映了它们独特和专门的组成和功能。
In the past 50 years, isolated blood platelets have had restricted use in wound healing, cancer therapy, and organ and tissue transplant, to name a few. The major obstacle for its unrestricted use has been, among others, the presence of ultrahigh concentrations of growth factors and the presence of both pro-angiogenic and anti-angiogenic proteins. To overcome this problem requires the isolation and separation of the membrane bound secretory vesicles containing the different factors. In the current study, high-resolution imaging of isolated secretory vesicles from human platelets using atomic force microscopy (AFM) and mass spectrometry enabled characterization of the remaining vesicles size and composition following their immunoseparation. The remaining vesicles obtained following osmotic lysis, when subjected to immunoseparation employing antibody to different vesicle-associated membrane proteins (VAMPs), demonstrate for the first time that VAMP-3-, VAMP-7-, and VAMP-8-specific vesicles each possesses distinct size range and composition. These results provide a window into our understanding of the heterogeneous population of vesicles in human platelets and their stability following both physical manipulation using AFM and osmotic lysis of the platelet. This study further provides a platform for isolation and the detailed characterization of platelet granules, with promise for their future use in therapy. Additionally, results from the study demonstrate that secretory vesicles of different size found in cells reflect their unique and specialized composition and function.
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影响因子: 7.4
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