Effect of trans‐resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function

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 μ M formyl methionyl leucyl phenylalamine (fMLP) (IC 50 1.3±0.13 μ M, 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 μ M, IC 50 18.4±1.8 and 31±1.8 μ M), and C5a (0.1 μ M, IC 50 41.6±3.5 and 42±8.3 μ M), and also inhibited elastase and β‐glucuronidase secretion (IC 50 37.7±7 and 25.4±2.2 μ M) and production of 5‐lipoxygenase metabolites leukotriene B 4 (LTB 4), 6‐trans‐LTB 4 and 12‐trans‐epi‐LTB 4 (IC 50 48±7 μ M) by PMN stimulated with the calcium ionophore A23187 (5 μ M). trans‐Resveratrol significantly reduced the expression and activation of the β 2 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. British Journal of Pharmacology (1998) 123, 1691–1699; doi:10.1038/sj.bjp.0701784