The internalization time course of a given lipopolysaccharide chemotype does not correspond to its activation kinetics in monocytes

The prerequisites for the initiation of pathophysiological effects of endot oxin (lipopolysaccharide [LPS]) include binding to and possibly internaliza tion by target cells. Monocytes/macrophages are prominent target cells whic h are activated by LPS to release various pro- and anti-inflammatory mediat ors. The aim of the present study was to establish a new method to determin e the binding and internalization rate of different LPS chemotypes by human monocytes and to correlate these phenomena with biological activity. It wa s found that membrane-bound LPS disappears within hours from the surface be ing internalized into the cell. Further, a correlation between the kinetics of internalization and the length of the sugar chain as well as an inverse correlation between the time course of internalization and LPS hydrophobic ity was revealed, Comparison of the internalization kinetics of different L PS chemotypes with kinetics of tumor necrosis factor alpha release and kine tics of oxidative burst did not reveal any correlation of these parameters. These findings suggest that cellular internalization of and activation by LPS are mechanisms which are independently regulated.