Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease
Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease
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DOI：
10.1053/gast.1997.v112.pm9178682
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发表时间：
1997-06-01
期刊：
影响因子：
29.4
通讯作者：
Fiocchi, C
中科院分区：
文献类型：
--
作者：
Binion, DG;West, GA;Fiocchi, C
背景和目的：微血管内皮细胞介导白细胞归巢、血管生成、炎症和愈合，并表现出组织特异性粘附分子和功能。在体外研究了人肠粘膜微血管内皮细胞（HIMEC）的激活，以揭示与炎症性肠病相关的可能异常。方法：从正常和炎症性肠病粘膜中分离 HIMEC，并评估其表型和形态特征、增殖反应、白细胞结合能力和粘附分子表达。结果：HIMEC 的基础增殖低于人脐静脉内皮细胞 (HUVEC)，但对血管内皮生长因子的反应按比例增加。促炎刺激诱导 HIMEC 单层细胞出现激活的纺锤形形态。与HUVEC相比，未刺激的HIMEC对U937和MOLT4细胞以及中性粒细胞的粘附力较低，但细胞因子和脂多糖显着增加了HIMEC的结合能力。源自炎症性肠病粘膜的 HIMEC 表现出比正常粘膜 HIMEC 明显更高的白细胞结合能力。 HIMEC、HUVEC 和粘膜间充质细胞中细胞间粘附分子 1、血管细胞粘附分子 1 和 E-选择素信使 RNA 的表达模式不同。结论：HIMEC 代表具有独特功能特性的分化内皮细胞。它们在炎症性肠病中结合白细胞的能力显着增强，表明 HIMEC 在引发或维持炎症中发挥着重要作用。
Background & Aims: Microvascular endothelial cells mediate leukocyte homing, angiogenesis, and inflammation and healing and show tissue-specific adhesion molecules and functions. The activation of human intestinal mucosal microvascular endothelial cells (HIMECs) was studied in vitro to uncover possible abnormalities associated with inflammatory bowel disease. Methods: HIMECs were isolated from normal and inflammatory bowel disease mucosa and assessed for phenotypic and morphological features, proliferative response, leukocyte binding capacity, and adhesion molecule expression. Results: Basal proliferation by HIMECs was less than that of human umbilical vein endothelial cells (HUVECs) but increased proportionally more in response to vascular endothelial growth factor. Proinflammatory stimuli induced an activated, spindle-shaped morphology in HIMEC monolayers. Compared with HUVECs, unstimulated HIMECs showed less adhesiveness for U937 and MOLT4 cells and neutrophils, but cytokines and lipopolysaccharide substantially increased the binding capacity of HIMECs. HIMECs derived from inflammatory bowel disease mucosa showed a markedly greater leukocyte-binding capacity than normal mucosal HIMECs. Patterns of intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and E-selectin messenger RNA expression were distinct in HIMECs, HUVECs, and mucosal mesenchymal cells. Conclusions: HIMECs represent differentiated endothelial cells with unique functional properties. Their dramatically enhanced capacity to bind leukocytes in inflammatory bowel disease suggests that HIMECs play an important role in initiating or maintaining inflammation.