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

1 Polymorphonuclear leukocytes (PMN) may contribute to the pathogenesis of acute coronary heart disease (CHD). 2 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. 3 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. 4 trans-Resveratrol exerted a strong inhibitory effect on reactive oxygen species produced by PMN stimulated with 1 mu M formyl methionyl leucyl phenylalamine (fMLP) (IC50 1.3+/-0.13 mu M, mean+/-s.e.mean), as evaluated by luminol-amplified chemiluminescence. 5 trans-Resveratrol prevented the release of elastase and beta-glucuronidase by PMN stimulated with the receptor agonists fMLP (1 mu M, IC50 18.4+/-1.8 and 31+/-1.8 mu M), and C5a (0.1 mu M, IC50 41.6+/-3.5 and 42+/-8.3 mu M), and also inhibited elastase and beta-glucuronidase secretion (IC50 37.7+/-7 and 25.4+/-2.2 mu M) and production of 5-lipoxygenase metabolites leukotriene B-4 (LTB4), 6-trans-LTB4 and 12-trans-epi-LTB4 (IC50 48+/-7 mu M) by PMN stimulated with the calcium ionophore A23187 (5 mu M). 6 trans-Resveratrol significantly reduced the expression and activation of the beta(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. 7 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.