MOLECULES AND STRUCTURES INVOLVED IN THE ADHESION OF NATURAL-KILLER-CELLS TO VASCULAR ENDOTHELIUM
MOLECULES AND STRUCTURES INVOLVED IN THE ADHESION OF NATURAL-KILLER-CELLS TO VASCULAR ENDOTHELIUM
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DOI：
10.1084/jem.173.2.439
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发表时间：
1991-02-01
影响因子：
15.3
通讯作者：
MANTOVANI, A
中科院分区：
文献类型：
--
作者：
ALLAVENA, P;PAGANIN, C;MANTOVANI, A
本研究的目的是确定参与自然杀伤（NK）细胞与血管内皮细胞在体外相互作用的分子和结构。静息和白细胞介素2（IL-2）激活的NK细胞的能力进行了研究，以坚持静息和IL-1处理的人脐静脉内皮细胞（EC）。在没有刺激的情况下，NK细胞表现出明显的粘附EC，与多晶型细胞和单核细胞之间的结合中间体的水平。用IL-2预处理NK细胞可增加其结合能力。使用适当的单克隆抗体，β-2白细胞整合素CD 18/CD 11 a被鉴定为NK细胞与未刺激EC的主要粘附途径。用IL-1激活EC增加NK细胞的结合。除了CD 18-CD 11 a/细胞间粘附分子途径外，静息或IL-2激活的NK细胞与IL-1激活的EC的相互作用涉及VLA-4（α-4-β-1）-血管细胞粘附分子1受体/反受体对。没有证据表明内皮细胞-白细胞粘附分子明显参与。通常，NK细胞通过从腹侧表面突出的点状粘附结构（podosomes）与培养基质或EC表面相互作用，该结构由粘着斑蛋白和talin环包围的F-肌动蛋白核心组成。识别NK细胞与EC相互作用中涉及的分子和显微解剖结构，可以更好地了解NK细胞从血液中募集、外渗和迁移到组织的调节。
The present study was designed to define molecules and structures involved in the interaction of natural killer (NK) cells with the vascular endothelium in vitro. Resting and interleukin 2 (IL-2)-activated NK cells were studied for their capacity to adhere to resting and IL-1-treated human umbilical vein endothelial cells (EC). In the absence of stimuli, NK cells showed appreciable adhesion to EC, with levels of binding intermediate between polymorphs and monocytes. The binding ability was increased by pretreatment of NK cells with IL-2. Using the appropriate monoclonal antibody, the beta-2 leukocyte integrin CD18/CD11a was identified as the major adhesion pathway of NK cells to unstimulated EC. Activation of EC with IL-1 increased the binding of NK cells. In addition to the CD18-CD11a/intercellular adhesion molecule pathway, the interaction of resting or IL-2-activated NK cells to IL-1-activated EC involved the VLA-4 (alpha-4-beta-1)-vascular cell adhesion molecule 1 receptor/counter-receptor pair. No evidence for appreciable involvement of endothelial-leukocyte adhesion molecule was obtained. Often, NK cells interacted either with the culture substrate or with the EC surface via dot-shaped adhesion structures (podosomes) protruding from the ventral surface and consisting of a core of F-actin surrounded by a ring of vinculin and talin. The identification of molecules and microanatomical structures involved in the interaction of NK cells with EC may provide a better understanding of the regulation of NK cell recruitment from blood, their extravasation, and their migration to tissues.