Endothelin-3
positive regulation of leukocyte chemotaxis
The involvement of protein kinase G in stimulation of neutrophil migration by endothelins.
Activation of human neutrophil migration by endothelin-1 and endothelin-3 is inhibited by guanylate cyclase inhibitors, by antagonists of protein kinase G (G-kinase), and by KT-5823, an inhibitor of G-kinase. Although no direct effect of endothelins on cGMP level could be established, these results suggest that the effect of these endothelins on migration is mediated by cGMP, and that the effect of cGMP proceeds via a G-kinase. There was little or no effect of guanylate cyclase inhibitors and G-kinase antagonists on endothelin-2-activated migration, indicating that the role of cGMP and G-kinase in endothelin-2-induced activation was either absent or at least different from that of the other endothelins. As compared with other activators, the role of G-kinase in formyl-methionyl-leucyl-phenylalanyl(fMLP-)activated migration resembled that of endothelin-activated migration, while the role of G-kinase in interleukin-8- or leukotriene B4-activated migration was less pronounced.