Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, Cincinnati, OH; and University of Cincinnati College of Medicine, Cincinnati, OH.
Blood. 2019 May 16;133(20):2149-2158. doi: 10.1182/blood-2018-12-844605. Epub 2019 Mar 21.
Neutrophils represent the first line of cellular defense against invading microorganism by rapidly moving across the blood-endothelial cell (EC) barrier and exerting effector cell functions. The neutrophil recruitment cascade to inflamed tissues involves elements of neutrophil rolling, firm adhesion, and crawling onto the EC surface before extravasating by breaching the EC barrier. The interaction between neutrophils and ECs occurs via various adhesive modules and is a critical event determining the mode of neutrophil transmigration, either at the EC junction (paracellular) or directly through the EC body (transcellular). Once thought to be a homogenous entity, new evidence clearly points to the plasticity of neutrophil functions. This review will focus on recent advances in our understanding of the mechanism of the neutrophil transmigration process. It will discuss how neutrophil-EC interactions and the subsequent mode of diapedesis, junctional or nonjunctional, can be context dependent and how this plasticity may be exploited clinically.
中性粒细胞通过快速穿过血管内皮细胞(EC)屏障并发挥效应细胞功能,成为抵御入侵微生物的第一道细胞防线。中性粒细胞向炎症组织的募集级联反应涉及中性粒细胞滚动、牢固黏附以及在穿过 EC 屏障之前在 EC 表面爬行等过程。中性粒细胞与 EC 之间的相互作用通过各种黏附模块发生,这是决定中性粒细胞迁移模式的关键事件,迁移模式要么通过 EC 连接(细胞旁),要么直接通过 EC 体(细胞间)。尽管中性粒细胞曾被认为是同质实体,但新的证据清楚地表明其功能具有可塑性。本文综述将重点介绍我们对中性粒细胞迁移过程机制的最新理解。它将讨论中性粒细胞-EC 相互作用以及随后的穿细胞脱逸模式(连接或非连接)如何依赖于上下文,以及这种可塑性如何在临床上得到利用。