Department of Surgery, University of Rochester Medical Center, Box SURG, 601 Elmwood Avenue, Rochester, NY 14642, USA.
OBJECTIVE: The aim of this study was to determine the effects of acetaldehyde on various steps of the monocyte recruitment cascade. METHODS: Human umbilical venous endothelial cells (HUVEC), primary blood monocytes (PBM) and THP-1 monocytes, were treated with acetaldehyde (0.1-0 microM) for 6h. Monocyte adherence experiments were performed using 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein-acetoxymethylester labeled PBM or (3)H-thymidine labeled THP-1 cells. HUVEC TNFalpha mRNA and protein levels were determined by quantitative real-time PCR and immunoassay, respectively, and HUVEC P-selectin and monocyte CCR2 expression were determined by FACS analysis. RESULTS: Acetaldehyde dose-dependently increased the number of CCR2 positive THP-1 monocytes, with a maximal increase of approximately 50% observed in the presence of 10 microM acetaldehyde. There was a significant increase in both the number of P-selectin positive cells and P-selectin receptor density when HUVEC were incubated with acetaldehyde. HUVEC TNFalpha mRNA expression and secretion were enhanced by acetaldehyde. Moreover, acetaldehyde increased THP-1 and PBM adhesion to HUVEC. Inhibition of P-selectin or TNFalpha, using antibodies or siRNA-directed gene knockdown, attenuated acetaldehyde-induced monocyte adhesion. In conclusion, acetaldehyde increased the number of CCR2 positive monocytes and stimulated endothelial cell P-selectin and TNFalpha expression. Moreover, acetaldehyde increased monocyte adhesion to endothelial cells, an effect that was both P-selectin- and TNFalpha-dependent. CONCLUSION: These effects of acetaldehyde may contribute, in part, to the increase in coronary heart disease that is associated with binge patterns of alcohol consumption.