Human monocytes have been demonstrated to generate endothelin-1 (ET-1) yet the role of this mediator in monocyte function has not been rigorously explored. Our research provides the first evidence that endothelin-1 (ET-1) may modulate monocyte adhesion by stimulation of nitric oxide (NO) release. The effects of ET-1 stimulation and NO release on monocyte adhesion was investigated using human peripheral blood monocytes and the human monocytic eell line, THP-1. Specific binding of 125I-labeled-ET-1 to monocytes was abrogated by pretreatment with the endothelin B (ETB) receptor antagonist, BQ-788, but not the endothelin A (ETA) receptor antagonist, BQ-123, consistent with predominant ETB receptor expression. Monocytes treated with ET-1 released nanomolar concentrations of NO as detected by an NO selective amperometric probe. Pretreatment with BQ-788 but not BQ-123 abrogated NO production, suggesting functional coupling of ETB receptors to NO release. Exposure of monocytes to ET-1 markedly attenuated adhesion of these cells to human saphenous vein whereas adhesion in the presence of BQ-788 was restored to that of control levels. These data demonstrate that monocyte interactions with the vascular wall can be reduced by autocrine production of NO and suggest that ETB receptors may attenuate monocyte activity at sites of inflammation.
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Molecular Biology