Myeloid Cells to the Rescue: Improving Thrombus Resolution
Myeloid Cells to the Rescue: Improving Thrombus Resolution
复制标题
骨髓细胞的救援：改善血栓溶解
DOI：
10.1055/s-0039-1701044
复制
发表时间：
2020
影响因子：
6.7
通讯作者：
Wenzel P.
中科院分区：
文献类型：
--
作者：
Knopp T;Karbach S;Wenzel P.
静脉血栓栓塞（VTE）包括深静脉血栓和肺栓塞，是世界上发病和死亡的主要原因之一。 1 如今的治疗意味着抗凝，这也使患者面临显着的出血风险。患有 VTE 的患者数量表明，该疾病的病理生理学尚未完全了解，必须进一步研究，以提供更好的预防和治疗策略并避免复发。在本期中，Kimball 等人致力于更好地了解单核细胞/巨噬细胞 (Mo/MΦ) 在血栓形成和消退中的作用。 2 他们能够证明，在腔静脉结扎的 VTE 小鼠模型中，毒素介导的 80% 至 90% CD11b+ Mo/MΦ 消耗对中性粒细胞募集、中性粒细胞胞外陷阱的形成和静脉血栓形成没有影响。虽然血栓形成未改变，但结扎后第 8 天，循环 CD11b+ Mo/MΦ 的消耗导致更大的血栓和血栓内纤溶功能受损。这种现象似乎是基于去除溶解血栓的主要细胞成分之一，即“修复性”Ly6Clo 单核细胞。为了检验他们的假设，CD11b+ Ly6Clo 单核细胞被过继转移到 Mo/MΦ 耗尽的小鼠中，导致血栓大小与未耗尽的对照相当。在他们的模型中，作者没有向我们提供血栓随时间消退的纵向数据。尽管如此，他们证实了早期的报告，该报告表明，使单核细胞表型偏离 Ly6Chi/IL-12+/T-bet+ 子集并随后减少干扰素 γ 形成可改善血栓溶解。 3-5 患有炎症性肠病或活动性自身免疫性疾病的个体，特别是当并发抗磷脂抗体综合征时，有发生 VTE 复发的风险。 1 对高敏感 C 反应蛋白增加的个体服用瑞舒伐他汀可减少症状性 VTE 的首次发生，6 表明减轻炎症负担可能是预防血栓形成的有效药物疗法。需要进一步的研究来证实基于增强骨髓细胞修复功能的免疫调节策略不仅可以改善愈合，还可以预防 VTE 复发。
Venous thromboembolism (VTE) comprising deep vein thrombosis and pulmonary embolism is one of the leading causes of morbidity and mortality in the world. 1 Therapy today means anticoagulation, which also puts the patient at significant bleeding risk. The number of patients afflicted by VTE indicates that pathophysiology of this disease is not yet fully understood and must be further investigated to provide better strategies for prevention and treatment and to avoid recurrence. In this issue, Kimball et al contribute to a better understanding of the role of monocytes/macrophages (Mo/MΦ) in thrombus formation and resolution. 2 They were able to show that toxin-mediated depletion of 80 to 90% of the CD11b+ Mo/MΦ had no effects on neutrophil recruitment, formation of neutrophil extracellular traps, and venous thrombus formation in a VTE mouse model of vena cava ligation. While thrombogenesis was unaltered, depletion of circulating CD11b+ Mo/MΦ resulted in larger thrombi and impaired intrathrombotic fibrinolysis at day 8 post ligation. This phenomenon seemed to be based on removing one of the main cellular components of a dissolving thrombus, the “reparative” Ly6Clo monocytes. To test their hypothesis, CD11b+ Ly6Clo monocytes were adoptively transferred into Mo/MΦ depleted mice, resulting in thrombus size comparable to nondepleted controls. In their model, the authors did not provide us with longitudinal data on thrombus resolution over time. Nevertheless, they corroborate earlier reports which showed that skewing the monocyte phenotype away from a Ly6Chi/IL-12+/T-bet+ subset with ensuing reduction of interferon gamma formation improves thrombus resolution. 3–5 Individuals suffering from inflammatory bowel disease or active autoimmune disease, in particular when complicated by antiphospholipid antibody syndrome, are at risk to experience VTE recurrence. 1 Rosuvastatin administered to individuals with increased high-sensitive C-reactive protein reduced first occurrence of symptomatic VTE, 6 suggesting that modification of the inflammatory burden might represent a valid drug therapy to prevent thrombosis. Further research will be needed to affirm that immunemodulatory strategies based on enhancing the reparative functions of myeloid cells will not only improve healing but also prevent recurrence of VTE.
影响因子：
4.6
作者：
Schönfelder T;Brandt M;Kossmann S;Knopp T;Münzel T;Walter U;Karbach SH;Wenzel P
通讯作者：
Wenzel P
影响因子：
20.1
作者：
Luther, Natascha;Shahneh, Fatemeh;Becker, Christian
通讯作者：
Becker, Christian
DOI：
10.1056/nejmoa0900241
发表时间：
2009-04-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Glynn RJ;Danielson E;Fonseca FA;Genest J;Gotto AM Jr;Kastelein JJ;Koenig W;Libby P;Lorenzatti AJ;MacFadyen JG;Nordestgaard BG;Shepherd J;Willerson JT;Ridker PM
通讯作者：
Ridker PM