Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Division of Internal Medicine, Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Cancer Metastasis Rev. 2022 Mar;41(1):147-172. doi: 10.1007/s10555-022-10019-5. Epub 2022 Jan 12.
We have established considerable expertise in studying the role of platelets in cancer biology. From this expertise, we were keen to recognize the numerous venous-, arterial-, microvascular-, and macrovascular thrombotic events and immunologic disorders are caused by severe, acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2) infections. With this offering, we explore the evolutionary connections that place platelets at the center of hemostasis, immunity, and adaptive phylogeny. Coevolutionary changes have also occurred in vertebrate viruses and their vertebrate hosts that reflect their respective evolutionary interactions. As mammals adapted from aquatic to terrestrial life and the heavy blood loss associated with placentalization-based live birth, platelets evolved phylogenetically from thrombocytes toward higher megakaryocyte-blebbing-based production rates and the lack of nuclei. With no nuclei and robust RNA synthesis, this adaptation may have influenced viral replication to become less efficient after virus particles are engulfed. Human platelets express numerous receptors that bind viral particles, which developed from archetypal origins to initiate aggregation and exocytic-release of thrombo-, immuno-, angiogenic-, growth-, and repair-stimulatory granule contents. Whether by direct, evolutionary, selective pressure, or not, these responses may help to contain virus spread, attract immune cells for eradication, and stimulate angiogenesis, growth, and wound repair after viral damage. Because mammalian and marsupial platelets became smaller and more plate-like their biophysical properties improved in function, which facilitated distribution near vessel walls in fluid-shear fields. This adaptation increased the probability that platelets could then interact with and engulf shedding virus particles. Platelets also generate circulating microvesicles that increase membrane surface-area encounters and mark viral targets. In order to match virus-production rates, billions of platelets are generated and turned over per day to continually provide active defenses and adaptation to suppress the spectrum of evolving threats like SARS-CoV-2.
我们在研究血小板在癌症生物学中的作用方面积累了丰富的专业知识。从这些专业知识中，我们敏锐地认识到，严重的急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染会导致许多静脉、动脉、微血管和大血管血栓形成事件和免疫紊乱。有鉴于此，我们探讨了将血小板置于止血、免疫和适应性系统发育中心的进化联系。脊椎动物病毒及其脊椎动物宿主也发生了共进化变化，反映了它们各自的进化相互作用。随着哺乳动物从水生动物向陆生动物的适应，以及与胎盘形成相关的活产导致的大量失血，血小板在系统发育上从血小板向更高的巨核细胞起泡为基础的更高产率和缺乏核的方向进化。由于缺乏核和强大的 RNA 合成，这种适应性可能影响病毒复制，使其在病毒颗粒被吞噬后效率降低。人类血小板表达多种受体，这些受体可以结合病毒颗粒，这些受体从原型起源发展而来，以启动聚集和血栓形成、免疫、血管生成、生长和修复刺激颗粒内容物的胞吐释放。无论是否通过直接的、进化的、选择性压力，这些反应可能有助于遏制病毒的传播，吸引免疫细胞进行清除，并在病毒损伤后刺激血管生成、生长和伤口修复。由于哺乳动物和有袋动物的血小板变得更小、更薄，其生物物理特性在功能上得到了改善，这使得它们在流体剪切场中更靠近血管壁分布。这种适应性增加了血小板与脱落病毒颗粒相互作用和吞噬的可能性。血小板还产生循环微泡，增加了膜表面积的接触，并标记病毒靶标。为了匹配病毒的产生率，每天会产生和更换数十亿个血小板，以持续提供积极的防御和适应性，以抑制 SARS-CoV-2 等不断发展的威胁的范围。
