Fractal-like kinetics of intracellular enzymatic reactions: a chemical framework of endotoxin tolerance and a possible non-specific contribution of macromolecular crowding to cross-tolerance

摘要

BackgroundThe response to endotoxin (LPS), and subsequent signal transduction lead to the production of cytokines such as tumor necrosis factor-α (TNF-α) by innate immune cells. Cells or organisms pretreated with endotoxin enter into a transient state of hyporesponsiveness, referred to as endotoxin tolerance (ET) which represents a particular case of negative preconditioning. Despite recent progress in understanding the molecular basis of ET, there is no consensus yet on the primary mechanism responsible for ET and for the more complex cases of cross tolerance. In this study, we examined the consequences of the macromolecular crowding (MMC) and of fractal-like kinetics (FLK) of intracellular enzymatic reactions on the LPS signaling machinery. We hypothesized that this particular type of enzyme kinetics may explain the development of ET phenomenon.