Growing Macrophages Regulate High Rates of Solute Flux by Pinocytosis

In metazoan cells, growth factors stimulate solute ingestion by pinocytosis. To examine the role of pinocytosis in cell growth, this study measured cell proliferation and the attendant rates of solute flux by pinocytosis in murine macrophages in response to the growth factor colony-stimulating factor-1 (CSF1). During CSF1-dependent growth in rich medium, macrophages internalized 72 percent of their cell volume in extracellular fluid every hour. Removal of the essential amino acid leucine from growth medium limited rates of protein synthesis and growth, but increased rates of solute accumulation by macropinocytosis. The amount of protein synthesized during leucine-dependent growth exceeded the capacity of pinocytosis to internalize enough soluble leucine to support growth and proliferation. Fluid-phase solute recycling from lysosomes secreted small molecules from the cells at high rates. Inhibitors of pinocytosis and the mechanistic target-of-rapamycin (mTOR) reduced cell growth and solute recycling, indicating roles for pinocytosis in growth and for nutrient sensing in the regulation of solute flux by pinocytosis. SummaryMurine macrophages growing in response to colony-stimulating factor-1 (CSF1) require pinocytosis. High rates of solute influx and accumulation by pinocytosis are regulated by CSF1 and leucine. Low molecular weight products of protein hydrolysis in lysosomes recycle efficiently from the cells.