Platelets Promote Macrophage Polarization toward Pro-inflammatory Phenotype and Increase Survival of Septic Mice
Platelets Promote Macrophage Polarization toward Pro-inflammatory Phenotype and Increase Survival of Septic Mice
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DOI：
10.1016/j.celrep.2019.06.062
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发表时间：
2019-07-23
期刊：
影响因子：
8.8
通讯作者：
Schattner, Mirta
中科院分区：
文献类型：
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作者：
Carestia, Agostina;Mena, Hebe A.;Schattner, Mirta
我们研究了脂多糖 (LPS) 存在下人血小板对巨噬细胞效应特性的贡献，以及脓毒症动物中血小板输注的有益效果和时间范围。我们的结果表明，血小板隔离单核细胞释放的促（TNF-α/IL-6）和抗（IL-10）炎症细胞因子。低 LPS 浓度 (0.01 ng/mL) 通过减少 CD64 并增加 CD206 和 CD163 表达诱导 M2 巨噬细胞极化；然而，血小板的存在通过糖蛋白 1b (GP1b)-CD11b 轴以细胞接触依赖性方式使单核细胞偏向 1 型巨噬细胞 (M1) 表型。因此，血小板许可的巨噬细胞显示出TNF-α水平增加、细菌吞噬活性增加以及愈合能力降低。血小板输注增加了诱导型一氧化氮合酶 (iNOS)(+) 巨噬细胞，提高了感染后 6 小时内脓毒症小鼠的细菌清除率和存活率，但 CD11b 和 GPIb 阻断消除了这一作用。我们的结果表明，血小板协调巨噬细胞效应反应，在狭窄但相关的时间范围内改善脓毒症的临床结果。
We investigated the contribution of human platelets to macrophage effector properties in the presence of lipopolysaccharide (LPS), as well as the beneficial effects and time frame for platelet transfusion in septic animals. Our results show that platelets sequester both pro-(TNF-alpha/IL-6) and anti-(IL-10) inflammatory cytokines released by monocytes. Low LPS concentrations (0.01 ng/mL) induced M2 macrophage polarization by decreasing CD64 and augmenting CD206 and CD163 expression; yet, the presence of platelets skewed monocytes toward type 1 macrophage (M1) phenotype in a cell-contact-dependent manner by the glycoprotein lb (GP1b)-CD11b axis. Accordingly, platelet-licensed macrophages showed increased TNF-alpha levels, bacterial phagocytic activity, and a reduced healing capability. Platelet transfusion increased inducible nitric oxide synthase (iNOS)(+) macrophages, improving bacterial clearance and survival rates in septic mice up to 6 h post-infection, an effect that was abolished by CD11b and GPIb blockade. Our results demonstrate that platelets orchestrate macrophage effector responses, improving the clinical outcome of sepsis in a narrow but relevant time frame.