Mevalonic acid (5 × 10-4 - 10-2 M) stimulates DNA synthesis in human peripheral blood lymphocytes which have been isolated by gravity sedimentation of blood and freed of adherent cells by nylon column passage. Human peripheral blood mononuclear cells isolated by the Ficoll-Hypaque technique respond less well, but their response to mevalonic acid can be enhanced by the neutrophil-rich Ficoll-Hypaque-isolated "bottom" cell fraction. The kinetics of mevalonic acid-induced lymphocyte transformation are similar to those of more classical lymphocyte mitogens. When measured by DNA synthesis, mevalonic acid is 1 6 as potent a mitogen as concanavalin A. Other organic acid anions, including those which serve as precursors of cholesterol and mevalonate biosynthesis, are devoid of such effects. Mevalonate-induced lymphocyte DNA synthesis is inhibited by hydroxyurea, but is independent of the supply of exogenous cholesterol. In addition to stimulating lymphocyte DNA synthesis mevalonic acid produces a population of cells representing all phases of the cell cycle whose morphological characteristics are typical of those seen with more conventional mitogens. The DNA synthetic response of lymphocytes to mevalonic acid can be abolished by prior exposure of the lymphocytes to X-irradiation or mitomycin C, while the helper effect of granulocytes is unaffected by either treatment.
ASJC Scopus subject areas
- Cell Biology