Characterization of endothelins as chemoattractants for human neutrophils.

The chemotactic response of human neutrophils to endothelins (ET) and ET-derived peptides was examined. ET-1, ET-2, and ET-3 elicited maximum responses at 10(-7), 3.3 x 10(-8) and 10(-7) M, respectively. Relative activities of the peptides at their optimal concentrations were: ET-1, ET-2 > ET-3. The chemotactic activity of ET-1 was localized to its Leu6-Met7-Asp8 segment. Conformation of the disulfide-linked Cys3-Cys11 loop appears to be critical for proper orientation of the chemotactic epitope. In comparison, ET-1 failed to stimulate the neutrophil respiratory burst, degranulation or arachidonic acid metabolism. These results demonstrate the selective chemoattractant activity of endothelins for human neutrophils.