Effect of trans-resveratrol,a natural polyphenolic compound,on human polymorphonuclear leukocyte function |
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Authors: | Serenella Rotondo Grazyna Rajtar Stefano Manarini Antonio Celardo Domenico Rotilio Giovanni de Gaetano Virgilio Evangelista Chiara Cerletti |
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Institution: | 1.Istituto di Ricerche Farmacologiche Mario Negri, ''G. Bizzozero'' Laboratory of Platelet and Leukocyte Pharmacology, Department of Vascular Medicine and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy;2.''G. Paone'' Environmental Health Center, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy |
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Abstract: | - Polymorphonuclear leukocytes (PMN) may contribute to the pathogenesis of acute coronary heart disease (CHD).
- Epidemiological and laboratory evidence suggests that red wine, by virtue of its polyphenolic constituents, may be more effective than other alcoholic beverages in reducing the risk of CHD mortality.
- The aim of the present study was to investigate the effects of trans-resveratrol (3,4′,5-trihydroxy-trans-stilbene), a polyphenol present in most red wines, on functional and biochemical responses of PMN, upon in vitro activation.
- trans-Resveratrol exerted a strong inhibitory effect on reactive oxygen species produced by PMN stimulated with 1 μM formyl methionyl leucyl phenylalamine (fMLP) (IC50 1.3±0.13 μM, mean±s.e.mean), as evaluated by luminol-amplified chemiluminescence.
- trans-Resveratrol prevented the release of elastase and β-glucuronidase by PMN stimulated with the receptor agonists fMLP (1 μM, IC50 18.4±1.8 and 31±1.8 μM), and C5a (0.1 μM, IC50 41.6±3.5 and 42±8.3 μM), and also inhibited elastase and β-glucuronidase secretion (IC50 37.7±7 and 25.4±2.2 μM) and production of 5-lipoxygenase metabolites leukotriene B4 (LTB4), 6-trans-LTB4 and 12-trans-epi-LTB4 (IC50 48±7 μM) by PMN stimulated with the calcium ionophore A23187 (5 μM).
- trans-Resveratrol significantly reduced the expression and activation of the β2 integrin MAC-1 on PMN surface following stimulation, as revealed by FACS analysis of the binding of an anti-MAC-1 monoclonal antibody (MoAb) and of the CBRM1/5 MoAb, recognizing an activation-dependent epitope on MAC-1. Consistently, PMN homotypic aggregation and formation of mixed cell-conjugates between PMN and thrombin-stimulated fixed platelets in a dynamic system were also prevented by trans-resveratrol.
- These results, indicating that trans-resveratrol interferes with the release of inflammatory mediators by activated PMN and down-regulates adhesion-dependent thrombogenic PMN functions, may provide some biological plausibility to the protective effect of red wine consumption against CHD.
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Keywords: | Coronary heart disease polymorphonuclear leukocytes toxic oxygen species proteolytic enzymes leukotriene B4 β 2 integrins MAC-1 cell adhesion red wine polyphenols trans-resveratrol |
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