Human neutrophil cytoskeletal dynamics and contractility actively contribute to trans-endothelial migration.
Human neutrophil cytoskeletal dynamics and contractility actively contribute to trans-endothelial migration.
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人类中性粒细胞细胞骨架动力学和收缩力积极促进跨内皮迁移。
DOI：
10.1371/journal.pone.0061377
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Aranda-Espinoza H
中科院分区：
文献类型：
--
作者：
Stroka KM;Hayenga HN;Aranda-Espinoza H
通过内皮细胞的迁移是免疫反应中的关键步骤。在我们最近的工作中，内皮下基质的力学性质和内皮细胞的生物物理状态已被确定为白细胞跨内皮细胞迁移的关键调节因素。在这里，我们证明了中性粒细胞收缩力量和细胞骨架动力学在通过内皮细胞-细胞连接的转运过程中也发挥着积极的生物物理作用。利用我们先前建立的白细胞迁移模型，我们首先发现，在我们的体外模型中，93%的人中性粒细胞优先使用细胞旁迁移模式，这与内皮下基质硬度无关。我们证明了肌动蛋白聚合或解聚的抑制完全阻止了转运，从而确立了中性粒细胞肌动蛋白动力学在转运中的关键作用。接下来，抑制中性粒细胞肌球蛋白II介导的收缩力量使44%的中性粒细胞在大多数中性粒细胞迁移后的几分钟内不能将其后缘收缩到内皮下。同时，抑制中性粒细胞收缩或稳定微管会使第一批中性粒细胞通过内皮完成转运的时间增加一倍。值得注意的是，随后的中性粒细胞通过与前一个中性粒细胞相同的路径，完成转运的时间显著减少，并且较少依赖中性粒细胞收缩力量和微管动力学。这些结果表明，第一个中性粒细胞诱导内皮细胞-细胞粘连的缝隙，这在内皮细胞中打开了门，并促进了随后的中性粒细胞通过同一孔的转归。总而言之，这项工作表明，中性粒细胞在免疫反应的轮回步骤中发挥着积极的生物物理作用。
Transmigration through the endothelium is a key step in the immune response. In our recent work, the mechanical properties of the subendothelial matrix and biophysical state of the endothelium have been identified as key modulators of leukocyte trans-endothelial migration. Here, we demonstrated that neutrophil contractile forces and cytoskeletal dynamics also play an active biophysical role during transmigration through endothelial cell-cell junctions. Using our previously-established model for leukocyte transmigration, we first discovered that >93% of human neutrophils preferentially exploit the paracellular mode of transmigration in our in vitro model, and that is independent of subendothelial matrix stiffness. We demonstrated that inhibition of actin polymerization or depolymerization completely blocks transmigration, thus establishing a critical role for neutrophil actin dynamics in transmigration. Next, inhibition of neutrophil myosin II-mediated contractile forces renders 44% of neutrophils incapable of retracting their trailing edge under the endothelium for several minutes after the majority of the neutrophil transmigrates. Meanwhile, inhibition of neutrophil contractile forces or stabilization of microtubules doubles the time to complete transmigration for the first neutrophils to cross the endothelium. Notably, the time to complete transmigration is significantly reduced for subsequent neutrophils that cross through the same path as a previous neutrophil and is less dependent on neutrophil contractile forces and microtubule dynamics. These results suggest that the first neutrophil induces a gap in endothelial cell-cell adhesions, which “opens the door” in the endothelium and facilitates transmigration of subsequent neutrophils through the same hole. Collectively, this work demonstrates that neutrophils play an active biophysical role during the transmigration step of the immune response.
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DOI：
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发表时间：
2002-06-24
期刊：
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影响因子：
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