The Anti Inflammatory Role of Lipoproteins

Ulevitch et al. were the first to observe that if LPS is mixed with serum or plasma, a decrease in buoyant density results. Pre-incubation of the LPS with the plasma decreased the ability of LPS to induce neutropenia and a pyrogenic response in rabbits. Further investigations showed that the LPS was bound to HDL and that a plasma protein aided in the binding. In rabbits, the uptake of LPS by the adrenal glands was increased after LPS binding to HDL, which indicates that binding of LPS to HDL results in a decreased recognition by LPS receptors. Since then, in vivo and in vitro experiments have shown that LPS and LTA bind to and are neutralized by lipid emulsions (90), chylomicrons (91), VLDL (92), LDL (92), 0HDL (92), apoAI (93), apoB (93), and apoE (94).

In vivo experiments have shown that the injection of LPS-HDL complexes may affect the serum decay of LPS and inhibits the LPS-induced release of cytokines when compared with LPS alone (91). In addition, in several experiments, the infusion of recombinant HDL (rHDL), VLDL, or lymph-derived chylomicrons and lipid emulsion also resulted in inhibition of LPS-induced physiological changes (95). Pajkrt et al. (96), in an experimental setting, infused rHDL into humans who were subsequently challenged with a low dose of LPS and observed a significant reduction in the release of proinflammatory cytokines and a partial reduction in the activation and/or release of components involved in coagulation. LDL receptor knockout mice, with cholesterol levels twice those in C57Bl6 mice, are less susceptible to LPS than wild-type mice, as shown by decreased mortality and reduced release of TNF, IL-1, and IL-6 (97). In contrast, the severely hypercholesterolemic apoE-knockout mice are more sensitive to LPS (98).

So far, only the binding of LPS to lipoproteins was discussed, but binding to apolipoproteins has also been reported. Emancipator et al. (93) and Usynin et al. have shown that both apoB and apoAI are able to bind and neutralize LPS. Our group has shown that LPS binds apoE and causes a redistribution in vivo, reducing the uptake by Kupffer cells and promoting the binding to liver parenchymal cells (94). In addition, we have also shown that apoE binds LTA resulting in a similar redistribution from Kupffer cells to liver parenchymal cells and in a strongly decreased TNF release in vivo (94).

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