Abstract
Leukocyte adhesion and trafficking at the endothelium requires both cellular adhesion molecules and chemotactic factors. A newly identified CX3C-chemokine, fractalkine, expressed on activated endothelial cells, plays an important role in leukocyte adhesion and migration. We found that THP-1 cells, expressing mRNA for fractalkine receptor, CX3CR 1 efficiently adhered to the membrane bound form of fractalkine expressed on ECV 304 cells or TNF-α-activated HUVECs. Soluble-fractalkine also enhanced adhesion of THP-1 cells to fibronectin and ICAM-1 in a dose dependent manner.
However, soluble fractalkine induced little chemotaxis in THP-1 cells in comparison to MCP -1 which induced a strong chemotactic response. Moreover, the membrane form of fractalkine expressed on ECV 304 cells reduced MCP-1-mediated chemotaxis of THP-1 cells. Furthermore, soluble fractalkine enhanced NK cell cytolytic activity against K 562 target cells by enhancing granular exocytosis. Transfection of fractalkine cDNA into ECV 304 cells or HUVECs resulted in increased susceptibility to NK cell-mediated cytolysis compared to control transfection. Together, these results indicate that fractalkine plays an important role not only in the binding of monocytes and NK cells to endothelial cells by enhancing integrin avidity, but also in NK cell-mediated endothelium damage, which may result in vascular injury.
