A factor in human plasma permits persistent expression of E-selectin by human endothelial cells.
E-selectin is an inducible endothelial cell adhesion protein that is a critical element in the binding of leukocytes to activated endothelial cells. It is induced by a variety of pro-inflammatory soluble substances including interleukin-1 (IL-1), tumor necrosis factor (TNF), or bacterial lipopolysaccharide (LPS). In vitro studies of a large vessel endothelial cells demonstrate that stimulation with TNF or IL-1 leads to a rapid, but transient, induction of E-selectin expression that disappears within 24 hours. However, in vivo studies have shown that microvascular endothelial cells persistently express E-selectin in chronic inflammatory states, particularly in the skin where it serves as a homing receptor for memory T cells. Stimulation of dermal-derived microvascular endothelial cells (HDMECs) with single doses of IL-1 alpha, TNF alpha, or LPS resulted in transient but slightly more persistent expression of E-selectin than seen after stimulation of large vessel derived umbilical vein endothelial cells (HUVECs). However, stimulation of either HDMECs or HUVECs with repetitive doses of IL-1 alpha, TNF alpha, or LPS in the presence of human serum or plasma resulted in persistent E-selectin expression in vitro. The persistent E-selectin cell surface expression was associated with persistent E-selectin mRNA expression and correlated with E-selectin-mediated HL-60 binding to endothelial cell monolayers. The effect of human plasma or serum was dose dependent, and fractionation of human plasma by gel filtration demonstrated that the E-selectin persistence activity resolved into high and low molecular peaks. These data demonstrate that human endothelial cells are capable of persistent E-selectin expression in vitro and that factors in human serum or plasma are critical in preventing cytokine refractoriness and loss of E-selectin expression. This study provides a basis to resolve the apparent discrepancies between previous in vivo and in vitro dynamics of E-selectin expression.
Sepp
N T
NT
Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia.
Gille
J
J
Li
L J
LJ
Caughman
S W
SW
Lawley
T J
TJ
Swerlick
R A
RA
D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000502:physiology*; D016207:Cytokines / Q000097:blood; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology*; D006801:Humans; D007375:Interleukin-1 / Q000097:blood*; D007942:Leukemia, Experimental; D007951:Leukemia, Myeloid; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D008833:Microcirculation / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D014471:Umbilical Veins / Q000737:chemistry
D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha