Stimulation of phosphatidylinositol turnover in the macrophage plasma membrane: a possible mechanism for signal transmission

The effect of various stimuli on the rate of phosphatidylinositol turnover by mouse peritoneal macrophages was studied by measuring the incorporation of myo-[2-³H]-inositol. It was found that the macrophage-activating agents endotoxin and Corynebacterium parvum caused an increase in phosphatidylinositol turnover whilst inert particles (Staphylococcus albus, latex and carbon) had no effect even though they were phagocytosed. The stimulation by C. parvum was dependent on the presence of T cells. T lymphocytes from normal mice and mice immunized with C. parvum were equally effective and it was found that both normal and immune T cells could be stimulated by C. parvum as indicated by an increased uptake of [6-³H]-thymidine. Supernatants from normal or immune spleen cells cultured with and without C. parvum were ineffective and could not replace intact T cells, indicating that cell to cell contact is required or a labile factor that acts over a short range. The time course of stimulation of phosphatidylinositol turnover by macrophages was studied using endotoxin. The rate of turnover increased slowly over a few hours and was still rising at 6 h but decreasing again at 24 h. The increase in bacteriostatic activity against Listeria monocytogenes by macrophages exposed to endotoxin took longer to develop and was more marked at 24 h than at 4 h. The differences between pathways leading to phagocytosis or chemotaxis and those resulting in activation are discussed.