Dexamethasone-Induced Change in the Sphingomyelin Content of Human Polymorphonuclear Leukocytes in Vitro*

Abstract

Human polymorphonuclear leukocytes were incubated with 8 × 10^-9 to 8 × 10^-5 M dexamethasone for 2 h. A significant increase in the sphingomyelin content of the cells was found when 8 × 10^-8 M dexamethasone was used, with lesser changes being noted when the concentration was increased or decreased from this level. The increase in the phospholipid was blocked by the addition of cycloheximide to the incubation. Concurrent with the increase in sphingomyelin, an increase in sphingomyelinase was demonstrated. This increased enzymatic activity may have occurred secondary to the increase in substrate or may be involved in the reverse reaction, whereby phosphorylcholine and ceramide combine to form sphingomyelin. Other studies have demonstrated an effect of corticosteroids to suppress the production of superoxide anion and the importance of a membrane oxidase in the production of the anion. An action of dexamethasone to both suppress superoxide anion production and increase sphingomyelin content suggests a possible effect of the lipid changes upon the oxidase responsible for the production of the anion.