Inhibitory effects of vitamin E on endothelial-dependent adhesive interactions with leukocytes induced by oxidized low density lipoprotein.
Leukocyte-endothelial cell interactions, which are mediated by various adhesion molecules, are a crucial event in inflammatory reactions including atherosclerosis. Alpha-tocopherol (alpha-Toc) has been used for protection and therapy of vascular diseases because of its antioxidant activity. The objective of the present study was to determine effect of alpha-Toc on endothelial-dependent adhesive interactions with leukocytes elicited by oxidized low density lipoprotein (oxLDL). Incubation of HUVEC with oxLDL (100 microg/mL) increased expression of proteins and messenger RNA of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on enzyme immunoassay and northern blotting assay; pretreatment with alpha-Toc reduced in a dose dependent manner. Adherence of polymorphonuclear leukocytes (PMN) or mononuclear leukocytes (MNC) to oxLDL-activated HUVEC was much increased compared with that to unstimulated HUVEC. Treatment of HUVEC with alpha-Toc, monoclonal antibody to ICAM-1 or VCAM-1 inhibited adherence of PMN or MNC in a dose dependent manner. These results suggest that alpha-Toc works as anti-atherogenic agent through inhibiting endothelial-dependent adhesive interactions with leukocytes induced by oxLDL.
Yoshida
N
N
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan. nyoshida@koto.kpu-m.ac.jp
Manabe
H
H
Terasawa
Y
Y
Nishimura
H
H
Enjo
F
F
Nishino
H
H
Yoshikawa
T
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins; D014810:Vitamin E / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014810:Vitamin E