Faculty Collaboration Database

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

Date

08/16/2003

Pubmed ID

12919942

DOI

10.1152/ajpgi.00484.2002

Scopus ID

2-s2.0-17544404890 (requires institutional sign-in at Scopus site)   35 Citations

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-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.

Author List

Rafiee P, Ogawa H, Heidemann J, Li MS, Aslam M, Lamirand TH, Fisher PJ, Graewin SJ, Dwinell MB, Johnson CP, Shaker R, Binion DG

Authors

Michael B. Dwinell PhD Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Christopher P. Johnson MD Professor in the Surgery department at Medical College of Wisconsin
Mona S. Li MD Assistant Professor in the Surgery department at Medical College of Wisconsin
Reza Shaker MD Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Adhesion
Cell Adhesion Molecules
Cell Separation
Cells, Cultured
Chemokines
Curcumin
Endothelium, Vascular
Enzyme Activation
Enzyme Inhibitors
Esophagitis
Esophagus
Humans
Immunoglobulins
Intestines
JNK Mitogen-Activated Protein Kinases
Leukocytes
Microcirculation
Mitogen-Activated Protein Kinases
Mucoproteins
NF-kappa B
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Phenotype
Signal Transduction
Vascular Cell Adhesion Molecule-1