Relaxin inhibits lipopolysaccharide-induced adhesion of neutrophils to coronary endothelial cells by a nitric oxide-mediated mechanism.
Neutrophil margination within blood vessels is an early finding during myocardial ischemia and can result in myocardial tissue injury. This phenomenon depends on the endothelial expression of adhesion molecules, which allow leukocyte extravasation. The hormone relaxin (RLX) was found to protect against experimental myocardial injury and to reduce neutrophil extravasation into the inflamed tissues. This study addresses the role of RLX in down-regulating endothelial adhesiveness to neutrophils and the possible involvement of NO, an anti-adhesive molecule, in the mechanism of action of RLX. Lipopolysaccharide (LPS)-primed rat coronary endothelial RCE) cells and neutrophils were co-cultured and their adhesion was quantified in the absence and presence of RLX, alone or together with the NO-synthase inhibitor L-NMMA. Inactivated RLX was used as control for specificity of the RLX effect. A 24-h incubation of LPS-primed RCE cells with RLX (60 and 600 ng/ml) caused a significant reduction of adherent neutrophils and of endothelial expression of the adhesion molecules P-selectin and VCAM-1 protein and mRNA, evaluated by immunohistochemistry, Western blot, and RT-PCR. These effects of RLX were blunted by L-NMMA and were not reproduced by inactivated RLX. These findings suggest that RLX has anti-inflammatory properties that could be of benefit in ischemic heart disease.
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D012065:Relaxin / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D008070:Lipopolysaccharides; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D009569:Nitric Oxide; D012065:Relaxin