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This Article Full Text Full Text (PDF) All Versions of this Article: 285/6/G1277    most recent 00484.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Rafiee, P. Articles by Binion, D. G. Search for Related Content PubMed PubMed Citation Articles by Rafiee, P. Articles by Binion, D. G.

INFLAMMATION/IMMUNITY/MEDIATORS

Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation

¹Departments of Surgery and ²Medicine, Division of Gastroenterology and Hepatology, Medical College of Wisconsin Dysphagia Institute, Digestive Disease Center, Milwaukee 53226; and ³Department of Microbiology and Molecular Genetics, Froedtert Memorial Lutheran Hospital, Milwaukee Veterans Affairs Medical Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Submitted 6 November 2002 ; accepted in final form 5 August 2003

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-/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-/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.

esophagus; esophagitis; gastroesophageal reflux disease; endothelium; microvascular; antioxidants; curcumin; nitric oxide; inflammation; vascular cell adhesion molecule-1; mucosal addressin cell adhesion molecule-1; stress-activated protein kinase/c-Jun NH₂-terminal kinase

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