TY - JOUR
T1 - Effect of trans-resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function
AU - Rotondo, Serenella
AU - Rajtar, Grazyna
AU - Manarini, Stefano
AU - Celardo, Antonio
AU - Rotilio, Domenico
AU - De Gaetano, Giovanni
AU - Evangelista, Virgilio
AU - Cerletti, Chiara
PY - 1998
Y1 - 1998
N2 - 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 μM formyl methionyl leucyl phenylalamine (fMLP) (IC50 1.3 ± 0.13 μM, mean ± s.e.mean), as evaluated by luminol-amplified chemiluminescence. 5. 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). 6. 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. 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.
AB - 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 μM formyl methionyl leucyl phenylalamine (fMLP) (IC50 1.3 ± 0.13 μM, mean ± s.e.mean), as evaluated by luminol-amplified chemiluminescence. 5. 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). 6. 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. 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.
KW - β integrins
KW - Cell adhesion
KW - Coronary heart disease
KW - Leukotriene B
KW - MAC-1
KW - Polymorphonuclear leukocytes
KW - Proteolytic enzymes
KW - Red wine polyphenols
KW - Toxic oxygen species
KW - Trans-resveratrol
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U2 - 10.1038/sj.bjp.0701784
DO - 10.1038/sj.bjp.0701784
M3 - Article
C2 - 9605577
AN - SCOPUS:15444353694
SN - 0007-1188
VL - 123
SP - 1691
EP - 1699
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 8
ER -