Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium.
BACKGROUND
Resveratrol is a phytoalexin present in red wine. It has been shown to protect LDL from peroxidative degradation.


OBJECTIVE
In consideration of the low plasma concentration of orally adsorbed resveratrol (which is insufficient for antioxidant protection of LDL), we studied another effect of the compound.


METHODS
Because resveratrol is a tyrosine kinase inhibitor like other members of the tyrphostin family, we hypothesized that it has the ability to modify intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression by stimulated endothelial cells. We studied the ability of resveratrol to inhibit such adhesion molecule expression and to block the adhesion of monocytes and granulocytes to endothelial cells.


RESULTS
We showed that resveratrol, at concentrations as low as 1 micromol/L and 100 nmol/L, significantly inhibited ICAM-1 and VCAM-1 expression by tumor necrosis factor alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells and lipopolysaccharide-stimulated human saphenous vein endothelial cells (HSVEC), respectively. In addition, we showed that resveratrol induced a significant inhibition in the adhesion of U937 monocytoid cells to lipopolysaccharide-stimulated HSVEC. Such inhibition was comparable with that obtained when anti-VCAM-1 monoclonal antibody was used instead of resveratrol. Resveratrol also significantly inhibited the adhesion of neutrophils to TNF-alpha-stimulated NIH/3T3 ICAM-1-transfected cells, whereas neutrophils activated by formyl-methionyl-leucyl-phenylalanine did not significantly modify adhesion to NIH/3T3 ICAM-1-transfected cells.


CONCLUSIONS
Our results indicate activity of resveratrol on endothelial cells and a new interpretation of an effect independent of its antioxidant function.
Ferrero
M E
ME
Institute of General Pathology, Centro di Studio sulla Patologia Cellulare del Consiglio Nazionale delle Ricerche, Milan, Italy. mefer@imiucca.csi.unimi.it
Bertelli
A E
AE
Fulgenzi
A
A
Pellegatta
F
F
Corsi
M M
MM
Bonfrate
M
M
Ferrara
F
F
De Caterina
R
R
Giovannini
L
L
Bertelli
A
A
D000975:Antioxidants / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D000077185:Resveratrol; D012501:Saphenous Vein; D013267:Stilbenes / Q000494:pharmacology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology
D000975:Antioxidants; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D013267:Stilbenes; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011505:Protein-Tyrosine Kinases; D000077185:Resveratrol