Memory T lymphocytes' adherence to Interferon gamma-activated human dermal microvascular endothelial cells via E-selectin

Abstract

The regulation of leukocytes-endothelial cells binding by biological response modifiers have an important role in determining the progression of acute and chronic inflammatory responses. In order to define the influence of E-selectin on the binding of T lymphocytes to human dermal microvascular endothelial cells (HDMEC), we examined the cell surface expression of E-selectin on HDMEC and the regulation of the binding of T lymphocytes to HDMEC by IFN-γ. We have demonstrated that stimulation of HDMEC with IL-1α or TNFα leads to transient E-selectin induction which disappears after 48 h, but stimulation of HDMEC with IFN-γ resulted in delayed E-selectin induction which was seen at 48 h of incubation and persisted until 72 h after stimulation. However, stimulation with IFN-γ failed to induce E-selectin expression on human umbilical vein endothelial cells. The delayed E-selectin expression on HDMEC by IFN-γ coincided with the increases in T lymphocyte binding to IFN-γ-activated HDMEC. The binding of memory T lymphocytes to IFN-γ-activated HDMEC was greater than that of naive T lymphocytes. Anti-E-selectin antibody partially inhibited memory T lymphocyte binding to HDMEC after 48 h of stimulation with IFN-γ. These data show that E-selectin expressions by IFN-γ on endothelial cells are regulated in a tissue-specific fashion and that E-selectin may be important in vivo in the preferential migration of memory T lymphocytes into inflammatory sites in the skin.