A novel bioactive 31-amino acid ET-1 peptide stimulates eosinophil recruitment and increases the levels of eotaxin and IL-5.
OBJECTIVE
Investigation of the role of a novel inflammatory mediator 31-amino acid endothelin-1 [ET-1 (1-31)], a major ET derivative in granulocytes, in eosinophil recruitment after its subcutaneous administration to mice.


METHODS
Various ET-1 derivatives (100 pmol), with or without ET receptor antagonists (200 pmol), were administered subcutaneously to mice, and then the eosinophil migration into and chemokine levels in the injected loci were analyzed.


RESULTS
ET-1 (1-31) and a 21-amino acid endothelin-1 (ET-1), but not big ET-1, induced eosinophil migration into the injected loci with a peak after administration for 12 h, and increased the levels of eotaxin and interleukin-5 with peaks at 6 and 24 h, respectively. These effects of ET-1(1-31) and ET-1 were significantly inhibited by an ETA receptor antagonist, BQ-123, but not by an ETB receptor antagonist, BQ-788.


CONCLUSIONS
Novel bioactive ET-1 (1-31) induces local eosinophil migration, and increases in eotaxin and interleukin-5 through an ETA or ETA-like receptor.
Sharmin
S
S
Division of Enzyme Chemistry, School of Medicine, The University of Tokushima, Japan.
Shiota
M
M
Murata
E
E
Cui
P
P
Kitamura
H
H
Yano
M
M
Kido
H
H
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000031:analogs & derivatives; D016232:Endothelins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007279:Injections, Subcutaneous; D015848:Interleukin-5 / Q000378:metabolism*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016207:Cytokines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D007202:Indicators and Reagents; D015848:Interleukin-5; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C114932:endothelin-1 (1-31); C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)