Inhibition of Stimulus-Specific Neutrophil Superoxide Generation by Alpha-Tocopherol

Abstract

Alpha-tocopherol but not 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (trolox or CTMC) and 2,2,5,7,8 pentamethyl-6-hydroxy chromane (PMC), derivatives of α-tocopherol, inhibited the superoxide (O₂⁻) generation of rat peritoneal neutrophils (RPMN) induced by phorbol 12-myristate 13-acetate (PMA). ID₅₀ for neutrophils obtained from the peritoneal cavity of rat and guinea pig was about 1μM. This concentration, however, was much lower than that for the inhibition of PMA-activated phospholipid-dependent protein kinase (PKC) (ID₅₀ = 30 μM). The α-tocopherol sensitive O₂⁻ generation was also observed in neutrophils induced by dioctanoylglycerol (diC₈) and calcium ionophore A23187 but not by formylmethionyl-leucyl-phenylalanine (FMLP), opsonized zymosan (OZ) and sodium dodecyl sulfate (SDS). The pattern of inhibition by α-tocopherol was quite similar to that of staurosporine, a specific inhibitor of PKC. The α-tocopherol content of RPMN was 12 ng/10⁶ cells and a linear increase to 200 ng/10⁶ cells by addition of α-tocopherol to the cell suspension corresponded with an increased inhibition of O₂⁻ generation. These results indicate that both the chemical structure and the content of α-tocopherol might be important factors in O₂⁻ generation by neutrophils.