A factor in human plasma permits persistent expression of E-selectin by human endothelial cells

Area of Science:

• Immunology
• Cell Biology
• Vascular Biology

Background:

• E-selectin is an inducible adhesion protein crucial for leukocyte binding to activated endothelial cells.
• Previous in vitro studies showed transient E-selectin expression, contrasting with persistent expression observed in vivo during chronic inflammation.

Purpose of the Study:

• To investigate the mechanisms behind persistent E-selectin expression in human endothelial cells in vitro.
• To reconcile discrepancies between in vitro and in vivo observations of E-selectin dynamics.

Main Methods:

• Stimulation of human dermal microvascular endothelial cells (HDMECs) and human umbilical vein endothelial cells (HUVECs) with inflammatory cytokines (IL-1 alpha, TNF alpha) and lipopolysaccharide (LPS).
• Assessment of E-selectin expression following single and repetitive stimulations, with and without human serum or plasma.
• Analysis of E-selectin mRNA levels and E-selectin-mediated cell binding assays (HL-60 cells).

Main Results:

• Repetitive stimulation with inflammatory agents in the presence of human serum or plasma induced persistent E-selectin expression in both HDMECs and HUVECs.
• Persistent surface expression correlated with sustained E-selectin mRNA levels and enhanced HL-60 cell adhesion.
• The effect of serum/plasma was dose-dependent, with active components identified at both high and low molecular weight fractions.

Conclusions:

• Human endothelial cells can exhibit persistent E-selectin expression in vitro under specific conditions.
• Factors present in human serum or plasma are critical for maintaining E-selectin expression and preventing cytokine refractoriness.
• This study provides a model to explain the differing E-selectin expression patterns observed in vitro and in vivo.