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Departments of 1 Surgery and 2 Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, Louisiana 71130
We compared U-937 cell adhesion and adhesion
molecule expression in human umbilical venous (HUVECs) and
arterial (HUAECs) endothelial cells exposed to tumor necrosis factor
(TNF), interleukin-1, and lipopolysaccharide (LPS). TNF and LPS
stimulated vascular cell adhesion molecule (VCAM)-1 surface expression
and adhesion of U-937 monocyte-like cells to HUVECs but not to HUAECs.
Antibody studies demonstrated that in HUVECs at least 75% of the
adhesion response is VCAM-1 mediated. Interleukin-1 stimulated U-937
cell adhesion to and VCAM-1 surface expression in both HUVECs and
HUAECs. Pyrrolidinedithiocarbamate and the proteasome inhibitor MG-132 blocked TNF- and LPS-stimulated U-937 cell adhesion to HUVECs. These
agents also significantly decreased TNF- and LPS-stimulated increases
in HUVEC surface VCAM-1. TNF increased VCAM-1 protein and mRNA in
HUVECs that was blocked by pyrrolidinedithiocarbamate. However, neither
TNF or LPS stimulated VCAM-1 expression in HUAECs. TNF stimulated
expression of both intercellular adhesion molecule-1 and E-selectin in
HUVECs, but in HUAECs, only intercellular adhesion molecule-1 was
increased. Electrophoretic mobility shift assays demonstrated no
difference in the pattern of TNF-stimulated nuclear factor-
B
activation between HUVECs and HUAECs. These studies demonstrate a novel
and striking insensitivity of arterial endothelium to the effects of
TNF and LPS and indicate a dissociation between the ability of HUAECs
to upregulate nuclear factor-
B and VCAM-1.
inflammatory mediators; cell culture; leukocyte-endothelial
interactions; E-selectin; vascular cell adhesion molecule-1; intercellular adhesion molecule-1; nuclear factor-
B
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