Abstract
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.
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