T-lymphocyte-derived tumor necrosis factor exacerbates anoxia-reoxygenation-induced neutrophil-endothelial cell adhesion.

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-alpha 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-alpha, which in turn elicits endothelial cell adhesion molecule expression and a corresponding increase in neutrophil adhesion.