alpha-Tocopherol enrichment of monocytes decreases agonist-induced adhesion to human endothelial cells.
BACKGROUND
Monocyte-endothelium adhesion is a crucial early event in atherogenesis. Several reports indicate that alpha-tocopherol (AT) is a potent antioxidant in plasma and LDL and also has intracellular effects that are antiatherogenic. Recently, it has been shown that AT supplementation results in decreased monocyte-endothelial cell adhesion. However, there is a paucity of data on the mechanisms by which AT inhibits adhesion of monocytes. We studied the effect of AT enrichment of a human monocytic cell line, U937, on adhesion to human umbilical vein endothelial cells (HUVECs).


RESULTS
Both lipopolysaccharide (LPS)- and N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated U937 adhesion to HUVECs were studied. AT (50 and 100 micromol/L) significantly decreased adhesion of both LPS- and FMLP-stimulated U937 cells to HUVECs (LPS-treated cells, P<0.0125; FMLP-treated cells, P<0.05). Expression of the adhesion molecules CD11a, CD11b, CD11c, very late antigen-4 (VLA-4), and L-selectin, as assessed by flow cytometry, was increased in the stimulated U937 cells, and AT resulted in significant reduction in the expression of CD11b and VLA-4. In addition, activation of the transcription factor nuclear factor-kappaB (NF-kappaB), as assessed by gel shift assays, was inhibited by pretreatment with AT in LPS-treated U937 cells.


CONCLUSIONS
AT significantly decreases adhesion of activated monocytes to endothelial cells by decreasing expression of CD11b and VLA-4 on monocytes, possibly by inhibiting the activation of NF-kappaB.
Islam
K N
KN
Departments of Pathology and Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Texas, USA.
Devaraj
S
S
Jialal
I
I
D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D020298:U937 Cells; D014810:Vitamin E / Q000494:pharmacology / Q000502:physiology*
D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014810:Vitamin E; D009240:N-Formylmethionine Leucyl-Phenylalanine