Endothelin‐1 enhances neutrophil adhesion to human coronary artery endothelial cells: role of ET_A receptors and platelet‐activating factor

Abstract

1 The potent coronary vasoconstrictor, endothelin-1 (ET-1) may also regulate neutrophil tra c 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 mM) 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 *83%. Increases in neutrophil adhesion evoked by ET-1 were also blocked by the platelet-activating factor (PAF) antagonists, BN 52021 (50 mM) and WEB 2086 (10 mM). 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 EC 50 values of *2 nM. These actions of ET-1 were almost completely prevented by the ET A receptor antagonist FR 139317 (1 mM) and the ET A /ET B receptor antagonist bosentan (10 mM), whereas the ET B receptor antagonist BQ 788 (1 mM) had no e ect. 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.

Loss of Mouse P2Y4 Nucleotide Receptor Protects against Myocardial Infarction through Endothelin-1 Downregulation

“…Among the proteins regulating the inflammatory response to cardiac ischemia, endothelin-1 (ET-1) plays an important role. Indeed ET-1 is involved in neutrophil trafficking and increases cardiac microvascular permeability (4,5). After the edema step, the healing process proceeds to the formation of granulation tissue, which is characterized by the presence of fibroblasts, macrophages, myofibroblasts, new blood vessels, and extracellular matrix proteins (6,7), ultimately resulting in scar formation, which is characterized by acellular and cross-linked collagen-rich regions (8)(9)(10)(11).…”

Relationship between no-reflow phenomenon and serotonin levels in patients with acute ST-elevation myocardial infarction who underwent primary percutaneous intervention

“…ET-l, the most abundant of the ET peptides in the cardiovascular system, is the most potent endogenous vasoconstrictor (26,27). It is also important modulator of neutrophil function and a stimulator of adhesion molecules (28,29). While increasing microvascular vasoconstriction and leukocytes adhesiveness to microvessel, ET-1 might aggravate noreflow.…”

Endothelin-1 Gene Polymorphisms rs5370, rs1476046, and rs3087459 are not Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus

“…41 Further, chronic infl ammation plays a key role in the development and progression of DN and ET-1 has been shown to exert a number of pro-infl ammatory effects. 41 It acts as a chemo-attractant for neutrophils 44 and monocytes 45 , and activates the endothelium to increase leucocyte adhesion and transmigration 46 , thus increasing leukocyte infi ltration within the kidney. Overexpression of human ET-1 in the kidney of transgenic mice induced prominent renal fi brosis that resulted in progressive decrease in glomerular fi ltration rate leading to fatal kidney disease.…”