Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1.
Cytokine-activated human endothelial monolayers support enhanced neutrophil transmigration via a mechanism involving both endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1.
复制标题
DOI：
10.4049/jimmunol.146.5.1617
复制
发表时间：
1991-03
影响因子：
4.4
通讯作者：
F. Luscinskas;M. Cybulsky;J. Kiely;Christopher S. Peckins;V. Davis;M. Gimbrone
中科院分区：
文献类型：
--
作者：
F. Luscinskas;M. Cybulsky;J. Kiely;Christopher S. Peckins;V. Davis;M. Gimbrone
rIL-1 β处理培养的人内皮细胞（HEC）促进多形核白细胞（PMN）粘附和迁移。使用在体外定量单层粘附和视频显微镜transmigration测定，我们已经研究了内皮细胞粘附分子-1（ELAM-1），细胞间粘附分子-1（ICAM-1），和白细胞粘附复合物，CD 11/CD 18，这些过程的贡献。rIL-1 β处理4 h后，ELAM-1的表面表达达到峰值，ICAM-1适度增加，观察到PMN粘附和迁移的最大增强。阻断针对ELAM-1或ICAM-1的mAb可抑制90%以上的上调PMN迁移。针对CD 11 a/CD 18（LFA-1，ICAM-1反受体）、CD 11b/CD 18（Mo-1）或CD 18（常见β 2-整联蛋白）的阻断mAb也阻断了90%以上的PMN迁移。在以后的时间点（24或48小时），ELAM-1的表面表达显着下降，而ICAM-1的表达增加超过4小时的水平，PMN粘附仍然升高（约50至60%的4小时水平），但迁移恢复到未活化的HEC的水平。这些数据表明，中性粒细胞与至少两种不同的HEC粘附分子的相互作用是必要的transendothelial迁移，并表明，中性粒细胞的粘附和transmigration，虽然相互关联，是机械上不同的过程。
rIL-1 beta treatment of cultured human endothelial cells (HEC) promotes polymorphonuclear leukocyte (PMN) adhesion and transmigration. Using in vitro quantitative monolayer adhesion and videomicroscopic transmigration assays, we have examined the contributions of endothelial-leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and the leukocyte adhesion complex, CD11/CD18, to these processes. Maximal enhancement of PMN adhesion and transmigration were observed after 4 h of rIL-1 beta treatment, when surface expression of ELAM-1 had peaked and ICAM-1 was modestly increased. Blocking mAb directed to either ELAM-1 or ICAM-1 inhibited greater than 90% of the up-regulated PMN transmigration. Blocking mAb directed to either CD11a/CD18 (LFA-1, a ICAM-1 counter-receptor), CD11b/CD18 (Mo-1), or CD18 (common beta 2-integrin) also blocked greater than 90% of PMN transmigration. At later time points (24 or 48 h), ELAM-1 surface expression was markedly decreased, whereas ICAM-1 expression was increased over the 4-h level; PMN adhesion remained elevated (approximately 50 to 60% of 4 h level), but transmigration returned to levels seen with unactivated HEC. These data indicate that PMN interaction with at least two distinct HEC adhesion molecules is necessary for transendothelial migration and suggests that PMN adhesion and transmigration, although interrelated, are mechanistically distinct processes.