Ley Klaus
Cardiovascular Research Center, University of Virginia Health System, Cardiovascular Research Center, Charlottesville, VA 22908-1394, USA.
Immunol Rev. 2002 Aug;186:8-18. doi: 10.1034/j.1600-065x.2002.18602.x.
In inflammation, neutrophils roll along the endothelial wall of postcapillary venules and sample inflammatory signals. Neutrophil activation is required to generate beta(2) integrin bonds with the endothelium that are strong enough to withstand the flow forces and thus achieve arrest from the rolling state. Unlike naïve T cells, neutrophils are not only activated by ligation of G-protein coupled receptors with chemokines and other chemoattractants but also receive signals from engagement of adhesion molecules including the selectins and beta(2) integrins. Rolling neutrophils integrate the sum total of inputs received while scanning the inflamed endothelium. In this process, the velocity of rolling neutrophils systematically decreases as a function of their contact time with the inflamed endothelium. If an activation threshold is reached, beta(2) integrins switch to the high-affinity conformation, redistribute on the cell surface, and trigger arrest and adhesion. Rolling cells that do not reach the activation threshold detach from the endothelium and are released back into the circulation. The role of chemokines, adhesion molecules, and other activating inputs involved in this response as well as signaling pathways are the subjects of ongoing investigations. This review provides a conceptual framework for neutrophil recruitment from the flowing blood.
在炎症反应中,中性粒细胞沿毛细血管后微静脉的内皮壁滚动并感知炎症信号。中性粒细胞需要被激活,以形成与内皮的β₂整合素键,这些键要足够强大,能够承受流动的力量,从而从滚动状态转变为停滞状态。与未活化的T细胞不同,中性粒细胞不仅通过G蛋白偶联受体与趋化因子及其他化学引诱剂的结合而被激活,还能从包括选择素和β₂整合素在内的黏附分子的相互作用中接收信号。滚动的中性粒细胞在扫描炎症内皮时整合接收到的所有输入信号。在此过程中,滚动的中性粒细胞的速度会随着其与炎症内皮接触时间的增加而系统性降低。如果达到激活阈值,β₂整合素会转变为高亲和力构象,在细胞表面重新分布,并引发停滞和黏附。未达到激活阈值的滚动细胞会从内皮脱离,重新释放回循环系统。趋化因子、黏附分子以及参与此反应的其他激活输入信号和信号通路的作用,仍是正在进行的研究课题。本综述为中性粒细胞从流动血液中的募集提供了一个概念框架。