Walter Brendel Centre of Experimental Medicine, University Hospital, and.
Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Ludwig-Maximilians-Universität München (LMU) Munich, Planegg-Martinsried, Germany.
Blood. 2018 Apr 26;131(17):1887-1898. doi: 10.1182/blood-2017-10-811851. Epub 2018 Feb 27.
Neutrophil extravasation and interstitial migration are important steps during the recruitment of neutrophils to sites of inflammation. In the present study, we addressed the functional importance of the unconventional class I myosin 1f (Myo1f) for neutrophil trafficking during acute inflammation. In contrast to leukocyte rolling and adhesion, the genetic absence of severely compromised neutrophil extravasation into the inflamed mouse cremaster tissue when compared with mice as studied by intravital microscopy. Similar results were obtained in experimental models of acute peritonitis and acute lung injury. In contrast to 2-dimensional migration, which occurred independently of Myo1f, Myo1f was indispensable for neutrophil migration in 3-dimensional (3D) environments, that is, transmigration and migration in collagen networks as it regulated squeezing and dynamic deformation of the neutrophil nucleus during migration through physical barriers. Thus, we provide evidence for an important role of Myo1f in neutrophil trafficking during inflammation by specifically regulating neutrophil extravasation and migration in 3D environments.
中性粒细胞外渗和间质迁移是中性粒细胞向炎症部位募集的重要步骤。在本研究中，我们研究了非传统 I 类肌球蛋白 1f（Myo1f）在急性炎症期间中性粒细胞迁移中的功能重要性。与白细胞滚动和黏附不同，与 相比，Myo1f 的基因缺失严重损害了中性粒细胞向炎症性鼠隐窝组织的外渗，这一点通过活体显微镜研究得到了证实。在急性腹膜炎和急性肺损伤的实验模型中也得到了类似的结果。与 2 维迁移不同，2 维迁移独立于 Myo1f 发生，而 Myo1f 对于 3 维（3D）环境中的中性粒细胞迁移是必不可少的，即穿越物理屏障时，中性粒细胞在胶原网络中的迁移和迁移，因为它调节了中性粒细胞核在迁移过程中的挤压和动态变形。因此，我们通过特异性调节 3D 环境中的中性粒细胞外渗和迁移，为 Myo1f 在炎症期间中性粒细胞迁移中的重要作用提供了证据。
