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.
Wright
C D
CD
Department of Immunopathology, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Cody
W L
WL
Dunbar
J B
JB
Doherty
A M
AM
Hingorani
G P
GP
Rapundalo
S T
ST
D000595:Amino Acid Sequence; D016718:Arachidonic Acid / Q000378:metabolism; D015550:Cell Degranulation; D002634:Chemotaxis, Leukocyte; D016232:Endothelins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008247:Lysosomes / Q000502:physiology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D016897:Respiratory Burst; D013329:Structure-Activity Relationship
D016232:Endothelins; D010446:Peptide Fragments; D016718:Arachidonic Acid