Micro-concentration Lipopolysaccharide as a Novel Stimulator of Megakaryocytopoiesis that Synergizes with IL-6 for Platelet Production.
Micro-concentration Lipopolysaccharide as a Novel Stimulator of Megakaryocytopoiesis that Synergizes with IL-6 for Platelet Production.
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微浓缩脂多糖作为巨核细胞生成的新型刺激剂，与 IL-6 协同促进血小板生成
DOI：
10.1038/srep13748
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发表时间：
2015-09-02
影响因子：
4.6
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Wu D;Xie J;Wang X;Zou B;Yu Y;Jing T;Zhang S;Zhang Q
脂多糖(LPS)可诱导血小板活化，增强血小板对聚集的敏感性，从而改变血小板数量。我们发现，在卡那霉素处理的小鼠中，一系列剂量的微量脂多糖显著增加了小鼠的血小板计数，同时也增加了小鼠骨髓巨核细胞中IL-6、IL-3和TPO的表达。此外，低浓度的内毒素加IL-6能有效地刺激CFU-MK的形成，增加CD41的表达和巨核细胞的多倍化。同时，小剂量内毒素联合IL-6可使小鼠全血网织血小板百分率持续升高。活体实验还表明，内毒素联合IL-6可显著增加正常小鼠和血小板减少小鼠外周血中循环血小板的数量。值得注意的是，最适浓度的内毒素和IL-6可能是一种新的TLR4和IL-6R在Dami细胞系中表达的刺激物，最初通过TLR4-IL-6R串扰发生，然后涉及到NF-κB的激活和p38MAPK的磷酸化。这些数据表明，通过内毒素和IL-6的协同作用来调节巨核细胞生成和血小板生成的新范式，有可能用于设计新的治疗方法。
Lipopolysaccharide (LPS) induces platelet activation and enhances platelet sensitivity to aggregation, which might alter platelet counts. We found that serial doses of micro-concentration LPS significantly increased the platelet count in mice treated with kanamycin, along with increased expression of IL-6 compared with IL-3 and TPO in megakaryocytes obtained from the mouse bone morrow following LPS administration. Furthermore, LPS at lower levels ranging plus IL-6 effectively stimulated CFU-MK formation and increased CD41 expression and megakaryocyte polyploidization. Meanwhile, there was a sustained rise in the percentage of reticulated platelets in the whole blood in response to low-dosage LPS combined with IL-6.In vivoexperiments also demonstrated that the administration of LPS combined with IL-6 substantially enhanced the number of circulating platelets in normal and thrombocytopenic mice. Notably, the optimal LPS concentration in combination with IL-6 might be a novel stimulator of TLR4 and IL-6R expression in Dami cell lines, which initially occurs through TLR4-IL-6R crosstalk and then involves the activation of NF-κB and phosphorylation of p38 MAPK. These data suggest a new paradigm for the regulation of megakaryocytopoiesis and platelet production via a synergistic effect of LPS and IL-6, which has the potential to be used for the design of new therapies.