Endothelin-1 enhances neutrophil adhesion to human coronary artery endothelial cells: role of ETAreceptors and platelet-activating factor
| Autor: | Chantal Baron, Alain Fournier, János G. Filep, Christine Zouki |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Pharmacology
ICAM-1 medicine.medical_specialty biology Platelet-activating factor Cell adhesion molecule medicine.drug_class Chemistry Receptor antagonist Endothelin 1 Molecular biology chemistry.chemical_compound Endocrinology Internal medicine E-selectin biology.protein medicine Endothelin receptor Receptor |
| Zdroj: | British Journal of Pharmacology. 127:969-979 |
| ISSN: | 0007-1188 |
| DOI: | 10.1038/sj.bjp.0702593 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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