Lipopolysaccharide regulates macrophage fluid phase pinocytosis via CD14-dependent and CD14-independent pathways

Lipopolysaccharide (LPS) is a mediator of inflammation and septic shock dur ing bacterial infection. Although monocytes and macrophages are highly resp onsive to LPS, the biological effects of LPS in these cell types are only p artially understood. We decided, therefore, to investigate the influence of LPS on macrophage pinocytosis and Fe receptor-mediated endocytosis, two pr ominent and related macrophage effector functions. We observed that LPS did not greatly influence endocytosis in either macrophages or monocytes, but did exert a dual action on pinocytosis: at lower concentrations (0.1 to 100 ng/mL), LPS caused a decrease in pinocytosis in both macrophages and monoc ytes, whereas at higher LPS concentrations, enhanced pinocytosis in macroph ages was observed. Detoxified LPS was two orders of magnitude less potent i n producing these effects. After inhibition of the LPS receptor CD14, the L PS-induced decrease in pinocytosis was absent, and stimulation of pinocytos is at lower LPS concentrations was unmasked. We conclude that LPS can influ ence pinocytosis via CD14-dependent and CD14-independent signaling pathways . Furthermore, as addition of LPS to macrophages effected pinocytosis but n ot Fc receptor-mediated endocytosis, these two processes are independently regulated in macrophages. (C) 1999 by The American Society of Hematology.