国际知名期刊《免疫》（Immunity）近期发表了华东师大生命科学研究院生命医学研究所教授王平与美国耶鲁大学教授Dan Wu合作的最新研究成果“整合素诱导的PIP5K1C激酶的极化调控中性粒细胞极性、方向选择及渗出”。
中性粒细胞（又称多形核嗜中性粒细胞），约占白细胞总数的50%～70%，是体内数量最多的白细胞。中性粒细胞在急性炎症中起着十分重要的作用，是机体抵御细菌入侵的第一道防线。通常，中性粒细胞在血液中循环或黏附于血管壁；另外，在骨髓中也储备有大量的中性粒细胞。当机体发生炎症时，炎症部位由病原体或受损细胞释放出化学趋化物，这些趋化物会形成浓度梯度，刺激中性粒细胞发生定向迁移，渗出血管到达炎症部位，进而消灭感染的病原微生物。中性粒细胞具有较强的吞噬能力，在炎症部位能够吞噬细菌等病原体，并通过细胞内的溶酶体等多种杀菌物质杀伤所感染细菌。另外，中性粒细胞所释放的各种酶也会对周围组织造成损伤而引发炎症反应。中性粒细胞渗出血管并定向迁移到炎症部位是一个复杂的生物学过程，也是炎症领域研究的重要研究方向之一。
PIP5K1C是细胞内产生磷脂肌醇PIP2的重要蛋白，参与多种细胞生物学功能。王平及合作者发现该蛋白在中性粒细胞的迁移中起重要作用：缺失PIP5K1C的中性粒细胞穿过血管壁到达炎症部位的能力明显下降。他们对这一现象的机制进行了深入研究，发现整合素信号能诱导该蛋白在中性粒细胞内极性分布。而整合素的活化对于中性粒细胞黏附与血管壁至关重要。他们发现该蛋白能通过调控化学信号对于小G蛋白RhoA及整合素的活化而调控中性粒细胞黏附于血管内皮细胞的能力。另外，他们还揭示了蛋白转运对于整合素诱导PIP5K1C-90在中性粒细胞内的极化是十分重要的。这项研究首次报道了整合素信号能够调控中性粒细胞的极性。
该研究得到了科技部、国家自然科学基金委以及上海市科委细胞信号网络平台及启明星计划的支持。王平与Dan Wu为共同通讯作者，华东师范大学为第一作者及通讯单位。（生物谷Bioon.com）
生物谷推荐原文出处：
Immunity doi:10.1016/j.immuni.2010.08.015
Integrin-Induced PIP5K1C Kinase Polarization Regulates Neutrophil Polarization, Directionality, and In Vivo Infiltration
Highlights
Integrin signaling confers mouse neutrophils a polarity
Integrin signaling polarizes PIP5K1C-90 localization
Integrin-regulated PIP5K1C-90 polarization mediates polarized RhoA activation
Integrin-regulated PIP5K1C-90 polarization is critical for neutrophil infiltration
Summary
Neutrophils are important in innate immunity and acute inflammatory responses. However, the regulation of their recruitment to sites of inflammation has not been well characterized. Here, we investigated the kinase PIP5K1C and showed that PIP5K1C deficiency impaired neutrophil recruitment because of an adhesion defect. PIP5K1C regulated the adhesion through facilitating RhoA GTPase and integrin activation by chemoattractants. Integrins could induce polarization of an isoform of PIP5K1C, PIP5K1C-90, in neutrophils through intracellular vesicle transport independently of exogenous chemoattractant. PIP5K1C-90 polarization was required for polarized RhoA activation at uropods and provided an initial directional cue for neutrophil polarization on the endothelium. Importantly, the polarization was also required for circumventing the inhibition of lamellipodium formation by RhoA so that neutrophils could form leading edges required for transendothelial migration. Because integrins are not known to regulate neutrophil polarization, our study revealed a previously underappreciated role of integrin signaling in neutrophil regulation.
