人體中的NK(Natural killer)細(xì)胞可自行識別并殺死發(fā)生病變的細(xì)胞,英國一項(xiàng)最新研究揭示了這種免疫細(xì)胞的敵我識別機(jī)制，解答了長期以來人們對其作用機(jī)制的疑惑,。
英國帝國理工學(xué)院的研究人員在新一期美國《公共科學(xué)圖書館·生物卷》月刊上報告說,，他們使用高速顯微鏡成像技術(shù)，觀測到NK細(xì)胞對所捕獲細(xì)胞作出“殺與不殺”抉擇的全過程,。
報告說,，NK細(xì)胞表面有許多受體感應(yīng)器，這些受體分為“激活”和“抑制”兩種,。當(dāng)它在人體內(nèi)捕獲一個可疑細(xì)胞后,，兩種受體將傳回不同的信號，如果是病變細(xì)胞,，“激活”信號大大增強(qiáng),，免疫細(xì)胞的“殺手本能”將被激活，從而殺死病變細(xì)胞,；反之,，如果捕獲的是一個健康細(xì)胞，“抑制”信號將占主導(dǎo)地位,，該細(xì)胞將會被釋放,。
NK細(xì)胞在殺傷靶細(xì)胞時不需要抗體參加，也不需要抗原預(yù)先致敏,。此前人們已經(jīng)知道它能夠在病變細(xì)胞和健康細(xì)胞之間作出“殺與不殺”的抉擇,，但并不了解其作用機(jī)制。（生物谷Bioon.com）
生物谷推薦原始出處：
PLoS Biol 7(7): e1000159. doi:10.1371/journal.pbio.1000159
Natural Killer Cell Signal Integration Balances Synapse Symmetry and Migration
Fiona J. Culley1¤a, Matthew Johnson1, J. Henry Evans1, Sunil Kumar1, Rupert Crilly1, Juan Casasbuenas1, Tim Schnyder1, Maryam Mehrabi1, Mahendra P. Deonarain1, Dmitry S. Ushakov2, Veronique Braud3, Günter Roth4, Roland Brock5¤b, Karsten K?hler1, Daniel M. Davis1*
1 Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom, 2 National Heart and Lung Institute, Imperial College London, London, United Kingdom, 3 Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique/Université de Nice-Sophia Antipolis, UMR6097, Valbonne, France, 4 Department of Molecular Biology, Interfacultary Institute for Cell Biology, University of Tübingen, Tübingen, Germany, 5 Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Natural killer (NK) cells discern the health of other cells by recognising the balance of activating and inhibitory ligands expressed by each target cell. However, how the integration of activating and inhibitory signals relates to formation of the NK cell immune synapse remains a central question in our understanding of NK cell recognition. Here we report that ligation of LFA-1 on NK cells induced asymmetrical cell spreading and migration. In contrast, ligation of the activating receptor NKG2D induced symmetrical spreading of ruffled lamellipodia encompassing a dynamic ring of f-actin, concurrent with polarization towards a target cell and a “stop” signal. Ligation of both LFA-1 and NKG2D together resulted in symmetrical spreading but co-ligation of inhibitory receptors reverted NK cells to an asymmetrical migratory configuration leading to inhibitory synapses being smaller and more rapidly disassembled. Using micropatterned activating and inhibitory ligands, signals were found to be continuously and locally integrated during spreading. Together, these data demonstrate that NK cells spread to form large, stable, symmetrical synapses if activating signals dominate, whereas asymmetrical migratory “kinapses” are favoured if inhibitory signals dominate. This clarifies how the integration of activating and inhibitory receptor signals is translated to an appropriate NK cell response.
