T-Lymphocyte–Derived Tumor Necrosis Factor Exacerbates Anoxia-Reoxygenation–Induced Neutrophil–Endothelial Cell Adhesion

Abstract

Abstract —The overall objective of this study was to determine whether T lymphocytes can modulate the increased neutrophil adherence and upregulation of endothelial cell adhesion molecules in human umbilical vein endothelial cells (HUVECs) exposed to anoxia/reoxygenation (A/R). HUVEC monolayers were exposed to 60 minutes of anoxia, followed by 4 hours of reoxygenation in the absence or presence of human T lymphocytes. The A/R-induced neutrophil adhesion was significantly enhanced when T lymphocytes and HUVECs were cocultured for the first 45 minutes of reoxygenation. This was accompanied by a more pronounced increase in E-selectin expression. When T lymphocytes were cocultured with HUVECs by use of inserts that prevented direct cell-cell contact, a comparable A/R-induced enhancement of neutrophil adhesion and of E-selectin expression was observed, indicating that soluble factors produced by T lymphocytes mediate the exaggerated A/R-induced inflammatory responses. Treatment with either an anti–tumor necrosis factor-α antibody or catalase attenuated the T-cell–mediated responses in postanoxic HUVECs. Moreover, the T-cell–mediated neutrophil adhesion response was mimicked by exposure of naive HUVECs to H 2 O 2. These findings indicate that H 2 O 2 produced by postanoxic endothelial cells stimulates T cells to produce tumor necrosis factor-α, which in turn elicits endothelial cell adhesion molecule expression and a corresponding increase in neutrophil adhesion.