Alpha‐tocopherol protects against monocyte Mac‐1 (CD11b/CD18) expression and Mac‐1‐dependent adhesion to endothelial cells induced by oxidized low‐density lipoprotein
Affiliations: First Department of Internal Medicine, Kyoto Prefectural University of Medicine, 465, Kajii‐cho, Kawaramachi, Hirokouji, Kamigyo‐ku, Kyoto 602‐0841, Japan
Note: [] Corresponding author: Norimasa Yoshida, M.D., Ph.D., First Department of Internal Medicine, Kyoto Prefectural University of Medicine, 465, Kajii‐cho, Kawaramachi, Hirokouji, Kamigyo‐ku, Kyoto 602‐0841, Japan. Tel.: +81 75 251 5505, Fax: +81 75 252 3721.
Abstract: α‐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 α‐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 μg/ml) increased Mac‐1 expression on monocytes, and preincubation with α‐tocopherol reduced this upregulation in a concentration dependent manner. In another experiment, whole blood was obtained from healthy adult volunteers after 10 days of α‐tocopherol administration (600 mg/day) and was incubated with oxidized LDL (100 μg/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 α‐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 α‐tocopherol was secondary to a decrease of protein kinase C activity. In conclusion, α‐tocopherol suppressed the upregulation of Mac‐1 expression on monocytes by oxidized LDL.
Keywords: α‐Tocopherol, Mac‐1, oxidized LDL, monocytes, protein kinase C
Journal: Biofactors, vol. 11, no. 4, pp. 221-233, 2000
