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

Parvaneh Rafiee, Hitoshi Ogawa, Jan Heidemann, Mona S. Li, Mohammed Aslam, Thomas H. Lamirand, Pamela J. Fisher, Shannon J. Graewin, Michael B. Dwinell, Christopher P. Johnson, Reza Shaker, David G. Binion

    Research output: Contribution to journalArticlepeer-review

    31 Citations (Scopus)

    Abstract

    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-α/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-α/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.

    Original languageEnglish
    JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
    Volume285
    Issue number6 48-6
    Publication statusPublished - 2003 Dec

    Keywords

    • Antioxidants
    • Curcumin
    • Endothelium
    • Esophagitis
    • Esophagus
    • Gastroesophageal reflux disease
    • Inflammation
    • Microvascular
    • Mucosal addressin cell adhesion molecule-1
    • Nitric oxide
    • Vascular cell adhesion molecule-1

    ASJC Scopus subject areas

    • Gastroenterology
    • Physiology

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