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 maximu m responses at 10(-7), 3.3 x 10(-8) and 10(-7) M, respectively. Relati ve 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 Leu(6)-Met(7)-Asp(8) segment. Conformation of the disulfide-linked Cy s(3) -Cys(11) loop appears to be critical for proper orientation of th e chemotactic epitope. In comparison, ET-1 failed to stimulate the neu trophil respiratory burst, degranulation or arachidonic acid metabolis m. These results demonstrate the selective chemoattractant activity of endothelins for human neutrophils.