Acetaldehyde stimulates monocyte adhesion in a P-selectin- and TNFalpha-dependent manner.
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.


CONCLUSIONS
These effects of acetaldehyde may contribute, in part, to the increase in coronary heart disease that is associated with binge patterns of alcohol consumption.
Redmond
Eileen M
EM
Department of Surgery, University of Rochester Medical Center, Box SURG, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Morrow
David
D
Kundimi
Sreenath
S
Miller-Graziano
Carol L
CL
Cullen
John P
JP
D000079:Acetaldehyde / Q000378:metabolism*; D000906:Antibodies; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D019007:P-Selectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; C515334:CCR2 protein, human; D019007:P-Selectin; D012333:RNA, Messenger; D054390:Receptors, CCR2; D014409:Tumor Necrosis Factor-alpha; D000079:Acetaldehyde