Garzon Dasgupta Andrei K, Martyanov Alexey A, Ignatova Anastasia A, Zgoda Victor G, Novichkova Galina A, Panteleev Mikhail A, Sveshnikova Anastasia N
Center for Theoretical Problems of Physico-Сhemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya str., Moscow, 109029, Russia.
National Medical Research Centеr of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, 1 Samory Mashela St, Moscow, 117198, Russia.
Pediatr Res. 2024 Mar;95(4):966-973. doi: 10.1038/s41390-023-02865-y. Epub 2023 Oct 23.
Platelets are blood cells responsible for the prevention of blood loss upon vessel wall disruption. It has been demonstrated that platelet functioning differs significantly between adult and pediatric donors. This study aimed to identify potential differences between the protein composition of platelets of pediatric, adolescent, and adult donors.
Platelet functional testing was conducted with live cell flow cytometry. Using a straightforward approach to platelet washing based on the sequential platelets centrifugation-resuspension, we were able to obtain stable and robust proteomics results, which corresponded to previously published data.
We have identified that pediatric donors' platelets have increased amounts of proteins, responsible for mitochondrial activity, proteasome activity, and vesicle transport. Flow cytometry analysis of platelet intracellular signaling and functional responses revealed that platelets of the pediatric donors have diminished granule secretion and increased quiescent platelet calcium concentration and decreased calcium mobilization in response to ADP. We could explain the observed changes in calcium responses by the increased mitochondria protein content, and the changes in granule secretion could be explained by the differences in vesicle transport protein content.
Therefore, we can conclude that the age-dependence of platelet functional responses originates from the difference in platelet protein content.
Platelets of infants are known to functionally differ from the platelet of adult donors, although the longevity and persistivity of these differences are debatable. Pediatric donor platelets have enhanced amounts of mitochondrial, proteasomal, and vesicle transport proteins. Platelets of the pediatric donors had increased cytosolic calcium in the resting state, what is explained by the increased numbers of mitochondrial proteins. Infants had decreased platelet granule release, which resolved upon adolescence. Thus, platelets of the infants should be assessed differently from adult platelets. Differences in platelet proteomic contents persisted in adolescent groups, yet, no significant differences in platelet function were observed.
血小板是负责在血管壁破裂时防止失血的血细胞。已证明成人和儿科供体的血小板功能存在显著差异。本研究旨在确定儿科、青少年和成人供体血小板蛋白质组成之间的潜在差异。
采用活细胞流式细胞术进行血小板功能测试。通过基于顺序血小板离心 - 重悬的直接血小板洗涤方法，我们能够获得稳定且可靠的蛋白质组学结果，这与先前发表的数据一致。
我们发现儿科供体的血小板中，负责线粒体活性、蛋白酶体活性和囊泡运输的蛋白质含量增加。血小板细胞内信号传导和功能反应的流式细胞术分析显示，儿科供体的血小板颗粒分泌减少，静息血小板钙浓度升高，对二磷酸腺苷（ADP）的钙动员减少。我们可以通过线粒体蛋白质含量的增加来解释观察到的钙反应变化，而颗粒分泌的变化可以通过囊泡运输蛋白质含量的差异来解释。
因此，我们可以得出结论，血小板功能反应的年龄依赖性源于血小板蛋白质含量的差异。
已知婴儿的血小板在功能上与成人供体的血小板不同，尽管这些差异的持久性和持续性存在争议。儿科供体血小板中线粒体、蛋白酶体和囊泡运输蛋白的含量增加。儿科供体的血小板在静息状态下胞质钙增加，这可以通过线粒体蛋白质数量的增加来解释。婴儿的血小板颗粒释放减少，这种情况在青春期得到解决。因此，婴儿的血小板应与成人血小板进行不同的评估。青少年组中血小板蛋白质组含量的差异仍然存在，但未观察到血小板功能的显著差异。
