Nieto M, Navarro F, Perez-Villar J J, del Pozo M A, González-Amaro R, Mellado M, Frade J M, Martínez-A C, López-Botet M, Sánchez-Madrid F
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
J Immunol. 1998 Oct 1;161(7):3330-9.
We report that the ability of NK cells to produce chemokines is increased in NK-target cell conjugates. The chemokines produced play a critical role in the polarization and recruitment of NK cells as well as in the NK effector-target cell conjugate formation. Chemokines induce the formation of two specialized regions in the NK cell: the advancing front or leading edge, where chemokine receptors CCR2 and CCR5 cluster, which might guide the cells toward the chemotactic source, and the uropod, where adhesion molecules ICAM-1 and -3 are redistributed. NK cell polarity was intrinsically involved in conjugate formation. The redistribution of both adhesion receptors and CCR was preserved during the formation of NK-target cell conjugates. Time-lapse videomicroscopy studies of the formation of effector-target conjugates showed that morphologic poles are also functionally distinct; while the binding to target cells was preferentially mediated through the leading edge, the uropod was found at the rear of migrating NK cells and recruited additional NK cells to the vicinity of K562 target cells. Inhibition of cell polarization and adhesion receptor redistribution blocked the formation of NK-K562 cell conjugates and the cytotoxic activity of NK cells. We discuss the implication of NK-cell polarization in the development of cytotoxic responses.
我们报道，在自然杀伤细胞（NK细胞）与靶细胞的结合物中，NK细胞产生趋化因子的能力增强。所产生的趋化因子在NK细胞的极化和募集以及NK效应细胞与靶细胞结合物的形成中发挥关键作用。趋化因子诱导NK细胞形成两个特殊区域：前进前沿或前缘，趋化因子受体CCR2和CCR5在此聚集，这可能引导细胞趋向趋化源；以及尾足，黏附分子ICAM-1和-3在此重新分布。NK细胞极性本质上参与了结合物的形成。在NK细胞与靶细胞结合物形成过程中，黏附受体和CCR的重新分布得以保留。对效应细胞与靶细胞结合物形成的延时视频显微镜研究表明，形态学上的两极在功能上也有所不同；虽然与靶细胞的结合主要通过前缘介导，但尾足位于迁移的NK细胞后部，并将更多NK细胞募集到K562靶细胞附近。抑制细胞极化和黏附受体重新分布会阻断NK-K562细胞结合物的形成以及NK细胞的细胞毒性活性。我们讨论了NK细胞极化在细胞毒性反应发展中的意义。
