Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Unidad de Investigación Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
Science. 2014 Dec 5;346(6214):1234-8. doi: 10.1126/science.1256478. Epub 2014 Dec 4.
Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. Consequently, neutrophils unable to polarize or to transduce signals through PSGL-1 displayed aberrant crawling, and blockade of this domain protected mice against thromboinflammatory injury. These results reveal that recruited neutrophils scan for activated platelets, and they suggest that the neutrophils' bipolarity allows the integration of signals present at both the endothelium and the circulation before inflammation proceeds.
免疫和炎症反应需要白细胞在血管内和血管中迁移,这一过程得益于它们能够转变为极化形态,使受体呈不对称分布。我们报告说,激活的静脉中的中性粒细胞极化有助于组织一个突出的区域,与存在于血液中的激活血小板结合。选择素配体 PSGL-1 转导这些相互作用产生的信号,导致驱动中性粒细胞迁移的受体重新分布。因此,不能极化或通过 PSGL-1 转导信号的中性粒细胞表现出异常的爬行,而阻断该区域可保护小鼠免受血栓炎症损伤。这些结果表明,募集的中性粒细胞会扫描激活的血小板,并且表明中性粒细胞的两极化允许在炎症发生之前整合存在于内皮细胞和循环中的信号。