Monocyte rolling, arrest and spreading on IL-4-activated vascular endothelium under flow is mediated via sequential action of L-selectin, beta 1-integrins, and beta 2-integrins.
Monocyte rolling, arrest and spreading on IL-4-activated vascular endothelium under flow is mediated via sequential action of L-selectin, beta 1-integrins, and beta 2-integrins.
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DOI：
10.1083/jcb.125.6.1417
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发表时间：
1994-06
期刊：
影响因子：
--
通讯作者：
Gimbrone MA Jr
中科院分区：
文献类型：
--
作者：
Luscinskas FW;Kansas GS;Ding H;Pizcueta P;Schleiffenbaum BE;Tedder TF;Gimbrone MA Jr
白细胞与血管内皮在炎症部位的相互作用可以通过激活依赖性粘附分子动态调节。目前的模型主要基于对多形核白细胞的研究，表明选择素、整合素和免疫球蛋白基因家族的多个成员依次参与了初始附着（滚动）、稳定粘附（阻滞）、扩散和最终脱落的过程。在当前的研究中，il -4激活的人脐静脉内皮选择性表达VCAM-1和l -选择素配体，但不表达E-选择素，以及适当的功能阻断单克隆抗体，用于在模拟微循环流动条件的体外模型中研究单核细胞-内皮相互作用。在这个系统中，L-选择素介导单核细胞滚动，也促进α - 4 - β - 1整合素依赖的阻滞，而β - 2整合素是在内皮细胞表面上牢固附着的单核细胞扩散所必需的，而不是它们的阻滞。这些发现为人类单核细胞在细胞因子激活的内皮上滚动提供了第一个体外证据，并表明在单核细胞-内皮相互作用中，β 1-和β 2-整合素依赖的粘附机制是顺序需要的。
Leukocyte interactions with vascular endothelium at sites of inflammation can be dynamically regulated by activation-dependent adhesion molecules. Current models, primarily based on studies with polymorphonuclear leukocytes, suggest the involvement of multiple members of the selectin, integrin, and immunoglobulin gene families, sequentially, in the process of initial attachment (rolling), stable adhesion (arrest), spreading and ultimate diapedesis. In the current study, IL-4-activated human umbilical vein endothelium, which selectively expresses VCAM-1 and an L-selectin ligand but not E- selectin, and appropriate function blocking monoclonal antibodies, were used to study monocyte-endothelial interactions in an in vitro model that mimics microcirculatory flow conditions. In this system, L- selectin mediates monocyte rolling and also facilitates alpha 4 beta 1- integrin-dependent arrest, whereas beta 2-integrins are required for spreading of firmly attached monocytes on the endothelial cell surface but not their arrest. These findings provide the first in vitro evidence for human monocyte rolling on cytokine-activated endothelium, and suggest a sequential requirement for both beta 1- and beta 2- integrin-dependent adhesive mechanisms in monocyte-endothelial interactions.