The Pinocytic Rate of Activated

Animals systemically infected with various intracellular parasites can show an increased ability to resist subsequent challenge with the same, or certain other, microorganisms . This resistant state is associated with a striking enhancement in the antimicrobial capacity of the fixed macrophages in the liver and spleen, as well as a family of physiologic and morphologic changes in the peritoneal macrophage population, which has been called "activation" (11) . These "activated" cells are larger, spread more rapidly on glass, have a larger complement of intracellular hydrolases (5), and display more plasma membrane activity than the resident peritoneal cells (2). A phenomenologically similar sort of "activation" has been accomplished by the intraperitoneal injection of endotoxin, thioglycollate medium, or proteose-peptone broth, among other materials. Since Lewis' morphologic observations (8), and subsequent observations by Cohn (4), it has been clear that the resident peritoneal macrophage has a striking and characteristic pinocytic capacity. With the development of a sensitive and reliable technique for measuring the pinocytic rate of cultured cells (13), it was possible to carry these analyses further, and to compare the activity of the macrophage with other cell types (14) . This method depends upon including, in the culture medium, the soluble enzyme horseradish peroxidase (HRP),' and then measuring the rate of accumulation of that enzyme within the cells. Previous work (6, 13) hasshownthat HRP is taken up by cells in the bulk phase, with little, if any, adsorption to the plasma membrane, and is included solely in membrane-bounded cytoplasmic vesicles by a temperature-sensitive, and energy-dependent process. Once interiorized, these HRP-containing pinosomes fuse with lysosomes, and the HRP is degraded with a half-life time of 8-10 h. Thus, over brief periods of time, up to 2 h, there is a linear accumulation of HRP in the cells which can be taken as an accurate measure of the volume of fluid pinocytosed during that time . We have studied the pinocytic activity of mouse peritoneal macrophages obtained after the intraperitoneal injection of several stimulating materials, in an effort to identify objective, quantitative differences between such cells and the resident macrophage population . Our studies show that pinocytic activity is