Rafiee Parvaneh, Ogawa Hitoshi, Heidemann Jan, Li Mona S, Aslam Mohammed, Lamirand Thomas H, Fisher Pamela J, Graewin Shannon J, Dwinell Michael B, Johnson Christopher P, Shaker Reza, Binion David G
Department of Surgery, Division of Gastroenterology and Hepatology, Medical College of Wisconsin Dysphagia Institute, Milwaukee 53226, USA.
Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1277-92. doi: 10.1152/ajpgi.00484.2002. Epub 2003 Aug 14.
Gastroesophageal reflux disease is the most common malady of the esophagus, affecting 7% of the United States population. Histological assessment demonstrates classic inflammatory mechanisms including selective leukocyte recruitment and hemorrhage, suggesting a prominent role for the microvasculature. We isolated and characterized human esophageal microvascular endothelial cells (EC) (HEMEC), examined inflammatory activation in response to cytokines, LPS, and acidic pH exposure, and identified signaling pathways that underlie activation. HEMEC displayed characteristic morphological and phenotypic features including acetylated LDL uptake. TNF-alpha/LPS activation of HEMEC resulted in upregulation of the cell adhesion molecules (CAM) ICAM-1, VCAM-1, E-selectin, and mucosal addressin CAM-1 (MAdCAM-1), increased IL-8 production, and enhanced leukocyte binding. Both acid and TNF-alpha/LPS activation lead to activation of SAPK/JNK in HEMEC that was linked to VCAM-1 expression and U-937 leukocyte adhesion. Expression of constitutive inducible nitric oxide synthase in HEMEC was in marked contrast to intestinal microvascular endothelial cells. In this study, we demonstrate that HEMECs are phenotypically and functionally distinct from lower gut-derived endothelial cells and will facilitate understanding of inflammatory mechanisms in esophageal inflammation.
胃食管反流病是食管最常见的疾病，影响着7%的美国人口。组织学评估显示出包括选择性白细胞募集和出血在内的典型炎症机制，提示微血管系统起重要作用。我们分离并鉴定了人食管微血管内皮细胞（HEMEC），检测了其对细胞因子、脂多糖和酸性pH暴露的炎症激活反应，并确定了激活背后的信号通路。HEMEC表现出包括乙酰化低密度脂蛋白摄取在内的特征性形态和表型特征。肿瘤坏死因子-α/脂多糖激活HEMEC导致细胞粘附分子（CAM）细胞间粘附分子-1（ICAM-1）、血管细胞粘附分子-1（VCAM-1）、E-选择素和黏膜地址素细胞粘附分子-1（MAdCAM-1）上调，白细胞介素-8产生增加，白细胞结合增强。酸和肿瘤坏死因子-α/脂多糖激活均导致HEMEC中应激活化蛋白激酶/应激活化的丝裂原活化蛋白激酶（SAPK/JNK）激活，这与VCAM-1表达和U-937白细胞粘附有关。HEMEC中组成型诱导型一氧化氮合酶的表达与肠道微血管内皮细胞形成显著对比。在本研究中，我们证明HEMEC在表型和功能上与来自下消化道的内皮细胞不同，这将有助于理解食管炎症中的炎症机制。
