來自耶魯大學(xué)，華東師大生命科學(xué)研究院生命醫(yī)學(xué)研究所的研究人員首次報道了整合素信號能夠調(diào)控中性粒細胞的極性,，發(fā)現(xiàn)了整合素誘導(dǎo)的PIP5K1C激酶能極化調(diào)控中性粒細胞極性,、方向選擇及滲出，這一研究成果公布在Cell旗下Immunity雜志上,。
文章由美國耶魯大學(xué)終身教授吳殿青研究組,，與華東師大生命科學(xué)研究院生命醫(yī)學(xué)研究所王平教授研究組共同完成，得到了國家科技部,、自然科學(xué)基金委以及上海市科委細胞信號網(wǎng)絡(luò)平臺及啟明星計劃的支持,。
中性粒細胞（也叫多形核嗜中性粒細胞），約占白細胞總數(shù)的50-70%,，是體內(nèi)數(shù)量最多的白細胞,。中性粒細胞在急性炎癥中起著十分重要的作用，是機體抵御細菌入侵的第一道防線,。通常,，中性粒細胞在血液中循環(huán)或粘附于血管壁；另外,，在骨髓中也儲備有大量的中性粒細胞,。當(dāng)機體發(fā)生炎癥時，炎癥部位由病原體或受損細胞釋放出化學(xué)趨化物,，這些趨化物會形成濃度梯度,，刺激中性粒細胞發(fā)生定向遷移,，滲出血管到達炎癥部位， 進而消滅感染的病原微生物,。中性粒細胞具有較強的吞噬能力,，在炎癥部位能夠吞噬細菌等病原體，并通過胞內(nèi)的溶酶體等多種殺菌物質(zhì)殺傷所感染細菌,。另外,，中性粒細胞所釋放出的各種酶也會對周圍組織造成損傷，而引發(fā)炎癥反應(yīng),。中性粒細胞滲出血管并定向遷移到炎癥部位是一個復(fù)雜的生物學(xué)過程,，也是炎癥領(lǐng)域研究的重要研究方向之一。
PIP5K1C是細胞內(nèi)產(chǎn)生磷脂肌醇PIP2的重要蛋白,，參與多種細胞生物學(xué)功能,。在這篇文章中，研究人員發(fā)現(xiàn)該蛋白在中性粒細胞的遷移中起重要作用：缺失PIP5K1C的中性粒細胞穿過血管壁到達炎癥部位的能力明顯下降,。他們對這一現(xiàn)象的機制進行了深入研究,，發(fā)現(xiàn)整合素信號能誘導(dǎo)該蛋白在中性粒細胞內(nèi)極性分布。而整合素的活化對于中性粒細胞粘附與血管壁至關(guān)重要,。他們發(fā)現(xiàn)該蛋白能通過調(diào)控化學(xué)信號對于小G蛋白RhoA及整合素的活化而調(diào)控中性粒細胞粘附于血管內(nèi)皮細胞的能力,。
另外，研究人員還揭示了蛋白轉(zhuǎn)運對于整合素誘導(dǎo)PIP5K1C-90在中性粒細胞內(nèi)的極化是十分重要的,。這項研究首次報道了整合素信號能夠調(diào)控中性粒細胞的極性,。（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
Authors
Wenwen Xu, Ping Wang, Bj?rn Petri, Yong Zhang, Wenwen Tang, Le Sun, Holger Kress, Thomas D. Manes, Yan Shi, Paul Kubes, Dianqing Wu
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.
