IL-15 is chemotactic for natural killer cells and stimulates their adhesion to vascular endothelium

IL-15 is chemotactic for natural killer cells and stimulates their adhesion to vascular endothelium
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DOI:
10.1002/jlb.61.6.729
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发表时间:
1997-06-01
影响因子:
5.5
通讯作者:
Mantovani, A
Mantovani, A
中科院分区:
医学3区
文献类型:
--
作者:
Allavena, P;Giardina, G;Mantovani, A

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白细胞介素-15(IL-15)是一种新近发现的细胞因子,具有IL-2样刺激T淋巴细胞和自然杀伤(NK)细胞的活性,IL-15通过IL-2受体的β链和γ链介导其功能。我们研究了IL-在趋化性测定中NK细胞的定向迁移和NK细胞与血管内皮结合的能力,IL-15(10-20 ng/mL)对新鲜分离的静息Nh细胞以及长期IL-2培养的Nh细胞具有趋化作用。棋盘格实验表明,仅在存在正梯度时观察到响应于IL-15的迁移用IL-15(10-20 ng/mL)过夜处理新鲜分离的Nh细胞增强了它们与体外培养的内皮细胞(EC)的结合,尤其是与静息EC的结合。IL-15激活的Nh细胞通过使用LFA-1/ICAM-1和VLA-4/VCAM-1粘附途径与静息和肿瘤坏死因子激活的EC结合,基本上与未处理的Nh细胞一样。IL-15增加Nh细胞与ICAM-1转染的NIH-3 T3成纤维细胞结合的事实,以及IL-15不增加与细胞外基质蛋白的结合的发现,其中涉及的主要分子是VLA蛋白,表明IL-15主要刺激LFA-1依赖性粘附。通过增加Nh细胞对血管内皮的粘附和迁移反应,IL-15是组织中Nh细胞募集的重要决定因素。
Interleukin-15 (IL-15) is a recently described cytokine with IL-2-like stimulating activities on T lymphocytes and natural killer (NK) cells, IL-15 mediates its function through the beta- and gamma-chains of the IL-2 receptor, In this work, we have investigated the effect of IL-15 on the directional migration of NK cells in chemotaxis assays and on the ability of NK cells to bind to vascular endothelium, IL-15 (10-20 ng/mL) had chemotactic effects on freshly isolated resting Nh cells as well as on long-termed IL-2-cultured Nh cells, A checkerboard experiment demonstrated that migration in response to IL-15 was observed only in the presence of a positive gradient (chemotaxis), Overnight treatment of freshly isolated Nh cells with IL-15 (10-20 ng/mL) augmented their binding to cultured endothelial cells (EC) in vitro, especially to resting EC. IL-15-activated Nh cells bound to resting and tumor necrosis factor-activated EC by use of LFA-1/ICAM-1 and VLA-4/VCAM-1 adhesion pathways, essentially as untreated Nh cells do, The fact that IL-15 increased Nh cell binding to ICAM-1-transfected NIH-3T3 fibroblasts, together with the finding that IL-15 did not increase binding to extracellular matrix proteins, where the major molecules involved are VLA proteins, indicated that IL-15 primarily stimulates LFA-1-dependent adhesion, By increasing Nh cell adhesion to vascular endothelium and migratory response, IL-15 is an important determinant of Nh cell recruitment in tissues.