William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
Nat Immunol. 2011 Jun 26;12(8):761-9. doi: 10.1038/ni.2062.
The migration of neutrophils into inflamed tissues is a fundamental component of innate immunity. A decisive step in this process is the polarized migration of blood neutrophils through endothelial cells (ECs) lining the venular lumen (transendothelial migration (TEM)) in a luminal-to-abluminal direction. By real-time confocal imaging, we found that neutrophils had disrupted polarized TEM ('hesitant' and 'reverse') in vivo. We noted these events in inflammation after ischemia-reperfusion injury, characterized by lower expression of junctional adhesion molecule C (JAM-C) at EC junctions, and they were enhanced by blockade or genetic deletion of JAM-C in ECs. Our results identify JAM-C as a key regulator of polarized neutrophil TEM in vivo and suggest that reverse TEM of neutrophils can contribute to the dissemination of systemic inflammation.
中性粒细胞向炎症组织的迁移是先天免疫的一个基本组成部分。在这个过程中，决定性的一步是血液中性粒细胞沿着血管腔内皮细胞（EC）的极化迁移（transendothelial migration (TEM)），从管腔到基底膜方向。通过实时共聚焦成像，我们发现中性粒细胞在体内已经破坏了极化的 TEM（“犹豫”和“反向”）。我们在缺血再灌注损伤后的炎症中观察到这些事件，其特征是 EC 连接处的连接黏附分子 C（JAM-C）表达降低，而在 EC 中阻断或基因敲除 JAM-C 则增强了这些事件。我们的结果表明 JAM-C 是体内极化中性粒细胞 TEM 的关键调节剂，并提示中性粒细胞的反向 TEM 可能有助于全身炎症的扩散。
