Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Via Salvatore Allende, 84081 Baronissi, Italy.
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.
Int J Mol Sci. 2023 Mar 1;24(5):4723. doi: 10.3390/ijms24054723.
SARS-CoV-2 infection causes a considerable inflammatory response coupled with impaired platelet reactivity, which can lead to platelet disorders recognized as negative prognostic factors in COVID-19 patients. The virus may cause thrombocytopenia or thrombocytosis during the different disease stages by destroying or activating platelets and influencing platelet production. While it is known that several viruses can impair megakaryopoiesis by generating an improper production and activation of platelets, the potential involvement of SARS-CoV-2 in affecting megakaryopoiesis is poorly understood. To this purpose, we explored, in vitro, the impact of SARS-CoV-2 stimulation in the MEG-01 cell line, a human megakaryoblastic leukemia cell line, considering its spontaneous capacity of releasing platelet-like particles (PLPs). We interrogated the effect of heat-inactivated SARS-CoV-2 lysate in the release of PLPs and activation from MEG-01, the signaling pathway influenced by SARS-CoV-2, and the functional effect on macrophagic skewing. The results highlight the potential influence of SARS-CoV-2 in the early stages of megakaryopoiesis by enhancing the production and activation of platelets, very likely due to the impairment of STATs signaling and AMPK activity. Overall, these findings provide new insight into the role of SARS-CoV-2 in affecting megakaryocyte-platelet compartment, possibly unlocking another avenue by which SARS-CoV-2 moves.
SARS-CoV-2 感染会引起相当大的炎症反应，同时伴有血小板反应性受损，这可能导致血小板紊乱，被认为是 COVID-19 患者的负面预后因素。病毒可能通过破坏或激活血小板以及影响血小板生成，在不同的疾病阶段导致血小板减少症或血小板增多症。虽然已知几种病毒可以通过产生不适当的血小板生成和激活来损害巨核细胞生成，但 SARS-CoV-2 潜在的影响巨核细胞生成的机制尚不清楚。为此，我们在体外探讨了 SARS-CoV-2 刺激对人类巨核母细胞白血病细胞系 MEG-01 的影响，考虑到其自发释放血小板样颗粒 (PLP) 的能力。我们研究了热灭活 SARS-CoV-2 裂解物对 MEG-01 中 PLP 释放和激活的影响、受 SARS-CoV-2 影响的信号通路以及对巨噬细胞偏斜的功能影响。结果突出了 SARS-CoV-2 在巨核细胞生成的早期阶段通过增强血小板的生成和激活可能产生的潜在影响，这很可能是由于 STATs 信号和 AMPK 活性受损所致。总的来说，这些发现为 SARS-CoV-2 影响巨核细胞-血小板区室的作用提供了新的见解，可能为 SARS-CoV-2 转移的另一种途径提供了启示。
