Alpha-tocopherol protects against monocyte Mac-1 (CD11b/CD18) expression and Mac-1-dependent adhesion to endothelial cells induced by oxidized low-density lipoprotein.
Alpha-tocopherol supplementation is reported to protect against cardiovascular disease and to influence cells involved in atherogenesis, such as monocytes. Interactions between monocytes and vascular endothelial cells occur early in atherogenesis, and adhesion is mediated by integrins. We evaluated the effects of alpha-tocopherol on expression of Mac-1 (CD11b/CD18) by monocytes after stimulation with oxidized low-density lipoprotein (LDL), which is implicated as a potent chemotactic agent in atherogenesis. Incubation of whole blood with oxidized LDL (100 microg/ml) increased Mac-1 expression on monocytes, and preincubation with alpha-tocopherol reduced this upregulation in a concentration dependent manner. In another experiment, whole blood was obtained from healthy adult volunteers after 10 days of alpha-tocopherol administration (600 mg/day) and was incubated with oxidized LDL (100 microg/ml). There was a decrease in the upregulation of Mac-1 compared with that measured before administration. Adherence of oxidized LDL-stimulated monocytes to human umbilical vein endothelial cells was reduced by pretreatment with alpha-tocopherol, and was also inhibited by an anti-CD18 monoclonal antibody. Experiments with protein kinase C inhibitors suggested that reduction of Mac-1 upregulation by alpha-tocopherol was secondary to a decrease of protein kinase C activity. In conclusion, alpha-tocopherol suppressed the upregulation of Mac-1 expression on monocytes by oxidized LDL.
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Y
Y
Terasawa
H
H
Manabe
N
N
Yoshida
M
M
Uemura
N
N
Sugimoto
Y
Y
Naito
T
T
Yoshikawa
M
M
Kondo
D000328:Adult; D018845:CD11 Antigens / Q000032:analysis* / Q000502:physiology; D018821:CD18 Antigens / Q000032:analysis / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D014471:Umbilical Veins; D014810:Vitamin E / Q000097:blood / Q000494:pharmacology*
D018845:CD11 Antigens; D018821:CD18 Antigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E; D011493:Protein Kinase C