CpG ODN 是合成的单链 DNA 序列，可作为免疫刺激剂。它们已越来越多地用于治疗多种癌症，然而，血小板减少症是某些序列的潜在公认副作用。我们测试了两种 CpG ODN（ODN 2395 和 ISIS 120704）在给予 BALB/c 小鼠时诱导血小板减少症的能力，并确定与血小板减少症相关的机制。对 BALB/c 小鼠进行预放血，然后注射滴定剂量的 CpG ODN，并测定血小板计数。对小鼠进行 IVIg 或各种 Toll 样受体 9 (TLR9​​) 和脾酪氨酸激酶 (Syk) 抑制剂和拮抗剂治疗，以确定它们对血小板减少症的影响。与盐水治疗的小鼠或用 2'-O- 治疗的小鼠相比甲氧基乙基 (MOE) 修饰的反义 (ASO) ODN，ODN 2395 和 ISIS 120704 分别在 3 小时和 24 小时内诱导急性剂量依赖性血小板减少症。血小板减少症与血浆单核细胞趋化蛋白 1 (MCP1) 显着增加相关。与 Syk 抑制剂或 TLR9 拮抗剂治疗一样，静脉注射免疫球蛋白 (IVIg) 显着缓解了 CpG ODN 诱导的血小板减少症。在体外，CpG ODN 可以激活人血小板，这与 THP-1 单核细胞增强的 IVIg 和 Syk 依赖性吞噬作用显着相关。这些结果表明，CpG ODN 诱导急性炎症相关（IVIg 敏感）血小板减少症，可通过 Syk 或 TLR9 阻断来缓解，并且 IVIg 和 Syk 依赖性血小板清除途径似乎是血小板减少症的主要原因。这些结果是否适用于人类仍有待阐明。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

CpG ODN are synthetic single stranded DNA sequences that act as immunostimulants. They have been increasingly used to treat several cancers, however, thrombocytopenia is a potential recognized side effect of some sequences.We tested the ability of two CpG ODN (ODN 2395 and ISIS 120704) to induce thrombocytopenia when administered to BALB/c mice and determined mechanisms associated with thrombocytopenia.BALB/c mice were pre-bled and then injected with titrated doses of CpG ODNs and platelet counts were determined. The mice were treated IVIg or with various inhibitors and antagonists of toll-like receptor 9 (TLR9) and spleen tyrosine kinase (Syk) to determine their effects on the thrombocytopenia.Compared with saline-treated mice or mice treated with 2'-O-methoxyethyl (MOE)-modified antisense (ASO) ODN, both ODN 2395 and ISIS 120704 induced an acute dose-dependent thrombocytopenia within 3 and 24 hours respectively. The thrombocytopenia was associated with significant increases in plasma monocyte chemoattractant protein 1 (MCP1). Intravenous immunoglobulin (IVIg) administration significantly rescued the CpG ODN-induced thrombocytopenia, as did treatment with either a Syk-inhibitor or TLR9 antagonists. In vitro, CpG ODN could activate human platelets and this correlated significantly with enhanced IVIg- and Syk-dependent phagocytosis by THP-1 monocytes. These results suggest that CpG ODN induce an acute inflammatory-associated (IVIg-sensitive) thrombocytopenia that can be alleviated by Syk- or TLR9-blockade, and an IVIg- and Syk-dependent platelet clearance pathway appears primarily responsible for the thrombocytopenia. Whether these results are applicable to humans still has to be elucidated.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.