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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Cell Separation
  • Cells, Cultured
  • Chemokines / metabolism
  • Curcumin / pharmacology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Esophagitis / etiology
  • Esophagus / blood supply*
  • Humans
  • Immunoglobulins / metabolism
  • Intestines / blood supply
  • JNK Mitogen-Activated Protein Kinases
  • Leukocytes / physiology
  • Microcirculation
  • Mitogen-Activated Protein Kinases / metabolism
  • Mucoproteins / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Phenotype
  • Signal Transduction
  • Vascular Cell Adhesion Molecule-1 / drug effects


  • Cell Adhesion Molecules
  • Chemokines
  • Enzyme Inhibitors
  • Immunoglobulins
  • MADCAM1 protein, human
  • Mucoproteins
  • NF-kappa B
  • Vascular Cell Adhesion Molecule-1
  • Nitric Oxide
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Curcumin