Chemotaxis of human blood monocytes toward endothelin-1 and the influence of calcium channel blockers.

The adherence of monocytes to the arterial endothelium followed by its migration into the arterial intima is the earliest event in atherogenesis. The vasoconstrictive peptide, Endothelin-1 (ET-1), is elevated in patients with atherosclerosis. We were interested to know whether ET-1 was a chemoattractant for blood monocytes. Using the modified membrane filter technique for chemotaxsis assessment, ET-1 increased monocyte chemotaxis in a dose-dependent manner. Ca2+ channel blockers, Nifedipine, Diltiazem and Verapamil (5 microM), reduced ET-1 chemotaxsis more than 60% (P < 0.001). Aspirin and Indomethacin (1 mM and 100 microM, respectively) reduced migration by 23% (P < 0.05). Alpha-Lipoic acid, Probucol and Neomycin (100 microM) were also migration inhibitory (37%, P < 0.01). These results suggest that ET-1 is a strong chemoattractant for blood monocytes; Ca2+ influx is probably the major stimulus for the accelerated migration induced by ET-1.