Endothelin-1 enhances neutrophil adhesion to human coronary artery endothelial cells: role of ET(A) receptors and platelet-activating factor.
Br J Pharmacol
; 127(4): 969-79, 1999 Jun.
Article
in En
| MEDLINE
| ID: mdl-10433505
ABSTRACT
1. The potent coronary vasoconstrictor, endothelin-1 (ET-1) may also regulate neutrophil traffic into tissues. The aim of the present study was to characterize the endothelin receptors responsible and to investigate the underlying mechanisms. 2. ET-1 (1 nM - 1 microM) markedly enhanced attachment of human neutrophils to lipopolysaccharide-, and to a lesser extent, to ET-1-activated human coronary artery endothelial cells (HCAEC). This can partially be blocked by monoclonal antibodies against E-selectin, L-selectin or CD18, whereas combination of the three antibodies inhibited adhesion by approximately 83%. Increases in neutrophil adhesion evoked by ET-1 were also blocked by the platelet-activating factor (PAF) antagonists, BN 52021 (50 microM) and WEB 2086 (10 microM). 3. ET-1 downregulated the expression of L-selectin and upregulated expression of CD11b/CD18 and CD45 on the neutrophil surface and induced gelatinase release with EC50 values of approximately 2 nM. These actions of ET-1 were almost completely prevented by the ET(A) receptor antagonist FR 139317 (1 microM) and the ET(A)/ET(B) receptor antagonist bosentan (10 microM), whereas the ET(B) receptor antagonist BQ 788 (1 microM) had no effect. ET-1 slightly increased the expression of E-selectin and ICAM-1 on HCAEC, that was prevented by BQ 788, but not by FR 139317. 4. Receptor binding studies indicated the presence of ET(B) receptors (KD 40 pM) on phosphoramidon-treated HCAEC and the predominant expression of ET(A) receptors (KD 38 pM) on neutrophils. 5. These results indicate that promotion by ET-1 of neutrophil adhesion to HCAEC is predominantly mediated through activation of ET(A) receptors on neutrophils and subsequent generation of PAF.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endothelium, Vascular
/
Platelet Activating Factor
/
Receptors, Endothelin
/
Endothelin-1
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Coronary Vessels
/
Neutrophils
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
Br J Pharmacol
Year:
1999
Document type:
Article
Affiliation country:
Canadá
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM