國(guó)際知名期刊《免疫》（Immunity）近期發(fā)表了華東師大生命科學(xué)研究院生命醫(yī)學(xué)研究所教授王平與美國(guó)耶魯大學(xué)教授Dan Wu合作的最新研究成果“整合素誘導(dǎo)的PIP5K1C激酶的極化調(diào)控中性粒細(xì)胞極性,、方向選擇及滲出”。
中性粒細(xì)胞（又稱(chēng)多形核嗜中性粒細(xì)胞）,，約占白細(xì)胞總數(shù)的50%～70%，是體內(nèi)數(shù)量最多的白細(xì)胞,。中性粒細(xì)胞在急性炎癥中起著十分重要的作用,，是機(jī)體抵御細(xì)菌入侵的第一道防線。通常,，中性粒細(xì)胞在血液中循環(huán)或黏附于血管壁,；另外，在骨髓中也儲(chǔ)備有大量的中性粒細(xì)胞,。當(dāng)機(jī)體發(fā)生炎癥時(shí),，炎癥部位由病原體或受損細(xì)胞釋放出化學(xué)趨化物，這些趨化物會(huì)形成濃度梯度,，刺激中性粒細(xì)胞發(fā)生定向遷移,，滲出血管到達(dá)炎癥部位，進(jìn)而消滅感染的病原微生物,。中性粒細(xì)胞具有較強(qiáng)的吞噬能力,，在炎癥部位能夠吞噬細(xì)菌等病原體，并通過(guò)細(xì)胞內(nèi)的溶酶體等多種殺菌物質(zhì)殺傷所感染細(xì)菌,。另外,，中性粒細(xì)胞所釋放的各種酶也會(huì)對(duì)周?chē)M織造成損傷而引發(fā)炎癥反應(yīng)。中性粒細(xì)胞滲出血管并定向遷移到炎癥部位是一個(gè)復(fù)雜的生物學(xué)過(guò)程,，也是炎癥領(lǐng)域研究的重要研究方向之一,。
PIP5K1C是細(xì)胞內(nèi)產(chǎn)生磷脂肌醇PIP2的重要蛋白，參與多種細(xì)胞生物學(xué)功能,。王平及合作者發(fā)現(xiàn)該蛋白在中性粒細(xì)胞的遷移中起重要作用：缺失PIP5K1C的中性粒細(xì)胞穿過(guò)血管壁到達(dá)炎癥部位的能力明顯下降,。他們對(duì)這一現(xiàn)象的機(jī)制進(jìn)行了深入研究，發(fā)現(xiàn)整合素信號(hào)能誘導(dǎo)該蛋白在中性粒細(xì)胞內(nèi)極性分布,。而整合素的活化對(duì)于中性粒細(xì)胞黏附與血管壁至關(guān)重要,。他們發(fā)現(xiàn)該蛋白能通過(guò)調(diào)控化學(xué)信號(hào)對(duì)于小G蛋白R(shí)hoA及整合素的活化而調(diào)控中性粒細(xì)胞黏附于血管內(nèi)皮細(xì)胞的能力。另外,，他們還揭示了蛋白轉(zhuǎn)運(yùn)對(duì)于整合素誘導(dǎo)PIP5K1C-90在中性粒細(xì)胞內(nèi)的極化是十分重要的,。這項(xiàng)研究首次報(bào)道了整合素信號(hào)能夠調(diào)控中性粒細(xì)胞的極性,。
該研究得到了科技部、國(guó)家自然科學(xué)基金委以及上海市科委細(xì)胞信號(hào)網(wǎng)絡(luò)平臺(tái)及啟明星計(jì)劃的支持,。王平與Dan Wu為共同通訊作者,，華東師范大學(xué)為第一作者及通訊單位。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
