Vitamin E protects against polymorphonuclear leukocyte-dependent adhesion to endothelial cells.
We evaluated the effects of alpha-Toc on surface expression of CD11b/CD18 on polymorphonuclear leukocytes (PMN) stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and oxidized low-density lipoprotein (oxLDL). Incubation of PMN with fMLP (1 microM) or oxLDL (100 microg/mL) increased CD11b/CD18 expression; pretreatment with alpha-Toc reduced in a dose-dependent manner. PMN obtained from healthy adults ingesting 600 mg alpha-Toc per day for 10 days were similarly incubated with fMLP or oxLDL; the surface level of CD11b/CD18 was inversely correlated with serum alpha-Toc concentrations. Adherence of PMN to human umbilical vein endothelial cells was increased by fMLP or oxLDL stimulation but reduced by alpha-Toc pretreatment or anti-CD18 monoclonal antibodies. cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) activity in PMN was also assayed. A PKC inhibitor, but not a PKA inhibitor, suppressed CD11b/CD18 up-regulation, and alpha-Toc slightly decreased fMLP- and oxLDL-induced activation of PKC. These results suggest that alpha-Toc may prevent inflammation by both reducing CD11b/ CD18 up-regulation and decreasing PMN-dependent adherence to EC.
Yoshida
N
N
First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan. nyoshida@koto.kpu-m.ac.jp
Yoshikawa
T
T
Manabe
H
H
Terasawa
Y
Y
Kondo
M
M
Noguchi
N
N
Niki
E
E
D018821:CD18 Antigens / Q000096:biosynthesis / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine / Q000494:pharmacology; D014471:Umbilical Veins; D015854:Up-Regulation / Q000187:drug effects; D014810:Vitamin E / Q000097:blood / Q000494:pharmacology*
D018821:CD18 Antigens; D008077:Lipoproteins, LDL; D016177:Macrophage-1 Antigen; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine