Molecular Medicine, National Heart and Lung Institute (NHLI), Imperial College, London, UK.
J Cell Sci. 2012 Apr 1;125(Pt 7):1652-6. doi: 10.1242/jcs.100438. Epub 2012 Feb 28.
Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killing. Here, we report that this process is regulated by the Rab27a GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a KO) neutrophils exhibit migration defects in vitro and in vivo, and live-cell microscopy suggests that delayed uropod detachment causes the migratory defect. Surface expression of CD11b, a key adhesion molecule, is increased in chemokine-stimulated Rab27a KO neutrophils compared with the control, suggesting a turnover delay caused by a defect in elastase secretion from azurophilic granules at the rear of bone marrow polymorphonuclear leukocytes (BM-PMNs). We suggest that Rab27a-dependent protease secretion regulates neutrophil migration through proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved in cell migration and invasion.
中性粒细胞的迁移对于免疫至关重要，并且先于诸如病原体杀伤等效应功能。在这里，我们报告称，该过程受到 Rab27a GTPase 的调节，该蛋白已知可控制颗粒胞吐作用。Rab27a 缺陷（Rab27a KO）中性粒细胞在体外和体内均表现出迁移缺陷，活细胞显微镜观察表明，尿足脱落延迟导致迁移缺陷。与对照相比，在趋化因子刺激的 Rab27a KO 中性粒细胞中，关键黏附分子 CD11b 的表面表达增加，这表明由于嗜苯胺蓝颗粒中的弹性蛋白酶从骨髓多形核白细胞（BM-PMN）的后部分泌缺陷而导致的周转率延迟。我们认为，Rab27a 依赖性蛋白酶分泌通过尿足的依赖于蛋白酶的去黏附来调节中性粒细胞迁移，该机制在细胞迁移和侵袭中可能是保守的。
