Mitogenic Properties of a Calcium Ionophore, A23187

Abstract

A23187 is a carboxylic antibiotic that selectively transfers calcium, magnesium, and other divalent cations across biologic membranes. This ionophore was found to produce morphologic blast transformation, DNA synthesis, and mitosis in human lymphocytes. Several hours of ionophore-cell contact were necessary to produce optimal mitogenesis. The effects were highly dependent on the presence of extracellular calcium and much less dependent on extracellular magnesium. Lanthanum chloride prevented the development of the observed ionophore effects. Results are consistent with the hypothesis that under physiologic conditions the interaction of antigens or mitogens with specific receptors at the lymphocyte membrane initiates events that alter calcium fluxes and result in increased cytoplasmic calcium. Increased cytoplasmic calcium is postulated to play a central role in the generation of surface-to-nuclear signals that initiate the process of DNA synthesis and cell division.