Vitamin E protects against polymorphonuclear leukocyte-dependent adhesion to endothelial cells

We evaluated the effects of a-Toe on surface expression of CD 11b/CD18 on p olymorphonuclear leukocytes (PMN) stimulated with N-formyl-methionyl-leucyl -phenylalanine (fMLP) and oxidized low-density lipoprotein (oxLDL). Incubat ion of PMN with fMLP (1 mu M) or oxLDL (100 mu g/mL) increased CD11b/CD18 e xpression; 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 CD11 b/CD18 was inversely correlated with serum alpha-Toc concentrations. Adhere nce of PMN to human umbilical vein endothelial cells was increased by fMLP or oxLDL stimulation but reduced by alpha-Toc pretreatment or anti-CD18 mon oclonal antibodies. cAMP-dependent protein kinase (PICA) and protein kinase C (PKC) activity in PMN was also assayed. A PKC inhibitor, but not a PICA inhibitor; suppressed CD11b/CD18 up-regulation, and alpha-Toc slightly decr eased fMLP- and oxLDL-induced activation of PKC. These results suggest that alpha-Toc may prevent inflammation by both reducing CD11b/ CD18 up-regulat ion and decreasing PMN-dependent adherence to EC.