Furie M B, Burns M J, Tancinco M C, Benjamin C D, Lobb R R
Department of Pathology, School of Medicine, State University of New York, Stony Brook 11794.
J Immunol. 1992 Apr 15;148(8):2395-404.
Treatment of vascular endothelial cells with inflammatory cytokines stimulates surface expression of E-selectin (previously known as endothelial-leukocyte adhesion molecule-1) and promotes the transendothelial migration of neutrophils. To assess participation of E-selectin in cytokine-mediated neutrophil migration, an in vitro model consisting of monolayers of human umbilical vein endothelial cells (HUVEC) grown on amniotic connective tissue was used. When HUVEC-amnion cultures were stimulated for 4 h with relatively low concentrations of IL-1 (0.1 to 0.15 U/ml), mAb BB11 or H18/7 to E-selectin partially inhibited migration of subsequently added neutrophils. However, when the cultures were stimulated with 15 U/ml of IL-1 for 4 or 24 h, little to no inhibition was observed. mAb to E-selectin also failed to inhibit migration of neutrophils across HUVEC-amnion cultures treated with low doses of IL-1 when the leukocytes were additionally stimulated by the chemoattractant leukotriene B4. In contrast, migration of neutrophils across IL-1-treated HUVEC was profoundly inhibited by mAb to CD11/CD18 leukocytic integrins under all conditions tested. Results of these studies suggest that participation of E-selectin is not essential for migration of neutrophils across cytokine-stimulated HUVEC in vitro; rather, E-selectin can be bypassed in favor of CD11/CD18-dependent mechanisms under appropriate circumstances.
用炎性细胞因子处理血管内皮细胞会刺激E-选择素（以前称为内皮细胞-白细胞黏附分子-1）的表面表达，并促进中性粒细胞的跨内皮迁移。为了评估E-选择素在细胞因子介导的中性粒细胞迁移中的作用，使用了一种体外模型，该模型由在羊膜结缔组织上生长的人脐静脉内皮细胞（HUVEC）单层组成。当用相对低浓度的IL-1（0.1至0.15 U/ml）刺激HUVEC-羊膜培养物4小时时，针对E-选择素的单克隆抗体BB11或H18/7部分抑制了随后添加的中性粒细胞的迁移。然而，当用15 U/ml的IL-1刺激培养物4或24小时时，几乎没有观察到抑制作用。当白细胞受到趋化因子白三烯B4额外刺激时，针对E-选择素的单克隆抗体也未能抑制中性粒细胞跨经低剂量IL-1处理的HUVEC-羊膜培养物的迁移。相反，在所有测试条件下，针对CD11/CD18白细胞整合素的单克隆抗体都能显著抑制中性粒细胞跨经IL-1处理的HUVEC的迁移。这些研究结果表明，E-选择素的参与对于体外中性粒细胞跨细胞因子刺激的HUVEC的迁移并非必不可少；相反，在适当情况下，可以绕过E-选择素而倾向于依赖CD11/CD18的机制。
