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Lipopolysaccharide regulates macrophage fluid phase pinocytosis via CD14-dependent and CD14-independent pathways
M P Peppelenbosch1, M DeSmedt, T ten Hove
1Laboratory for Experimental Internal Medicine, G2-130 Academic Medical Centre, Amsterdam, The Netherlands. M.P.Peppelenbosch@AMC.UVA.NL
Abstract:
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.
Insights
Lipopolysaccharide (LPS) affects macrophage pinocytosis through dual pathways. Lower LPS concentrations decrease pinocytosis, while higher concentrations enhance it, involving CD14-dependent and independent signaling.
Area of Science:
- Immunology
- Cell Biology
Background:
- Lipopolysaccharide (LPS) is a key mediator of inflammation and septic shock in bacterial infections.
- Monocytes and macrophages are crucial immune cells highly responsive to LPS, but its precise effects on their functions are not fully understood.
Purpose of the Study:
- To investigate the influence of LPS on macrophage pinocytosis and Fc receptor-mediated endocytosis.
- To elucidate the signaling pathways involved in LPS-mediated effects on macrophage functions.
Main Methods:
- Assessing pinocytosis and Fc receptor-mediated endocytosis in macrophages and monocytes exposed to varying LPS concentrations.
- Utilizing detoxified LPS to evaluate the role of endotoxin activity.
- Investigating LPS effects after inhibiting the LPS receptor CD14.
Main Results:
- LPS showed minimal influence on Fc receptor-mediated endocytosis but exerted a dual effect on pinocytosis.
- Lower LPS concentrations (0.1-100 ng/mL) decreased pinocytosis in both cell types.
- Higher LPS concentrations enhanced pinocytosis in macrophages, an effect dependent on CD14 signaling.
- CD14 inhibition unmasked LPS-induced pinocytosis stimulation at lower concentrations.
Conclusions:
- LPS influences macrophage pinocytosis through both CD14-dependent and CD14-independent pathways.
- Pinocytosis and Fc receptor-mediated endocytosis are independently regulated processes in macrophages.
- Understanding these pathways is crucial for managing inflammatory responses in bacterial infections.