Lipopolysaccharide regulates macrophage fluid phase pinocytosis via CD14-dependent and CD14-independent pathways.
Lipopolysaccharide (LPS) is a mediator of inflammation and septic shock during bacterial infection. Although monocytes and macrophages are highly responsive to LPS, the biological effects of LPS in these cell types are only partially understood. We decided, therefore, to investigate the influence of LPS on macrophage pinocytosis and Fc receptor-mediated endocytosis, two prominent 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 monocytes, whereas at higher LPS concentrations, enhanced pinocytosis in macrophages was observed. Detoxified LPS was two orders of magnitude less potent in producing these effects. After inhibition of the LPS receptor CD14, the LPS-induced decrease in pinocytosis was absent, and stimulation of pinocytosis at lower LPS concentrations was unmasked. We conclude that LPS can influence pinocytosis via CD14-dependent and CD14-independent signaling pathways. Furthermore, as addition of LPS to macrophages effected pinocytosis but not Fc receptor-mediated endocytosis, these two processes are independently regulated in macrophages.
Peppelenbosch
M P
MP
Laboratory for Experimental Internal Medicine, G2-130 Academic Medical Centre, Amsterdam, The Netherlands. M.P.Peppelenbosch@AMC.UVA.NL
DeSmedt
M
M
ten Hove
T
T
van Deventer
S J
SJ
Grooten
J
J
D000818:Animals; D002478:Cells, Cultured; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D010873:Pinocytosis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides