Apolipoproteins inhibit the innate immunity activated by necrotic cells or bacterial endotoxin

We suggested earlier that the hydrophobic portions (Hyppos) of molecules, which are normally embedded in the membranes of cells or the core of molecular structures so as to be separated from the aqueous environment, might serve as evolutionarily ancient alarm signals of injury or stress to initiate innate immune responses when they are exposed on the surface. Under normal physiological conditions, the Hyppos released from endogenous or exogenous sources might be handled by 'Hyppo-quenchers'in vivo to maintain the tissue homeostasis and immune modulation. To test this idea, we selected apolipoproteins, which have been known to transport blood lipids and play a role in a number of pathological inflammatory conditions. We examined their role as Hyppo-quenchers in early immune responses and found that apolipoproteins showed significant inhibition of the nuclear factor-kappaB-dependent gene expression in recombinant Chinese hamster ovary (CHO) cells and dendritic cells stimulated by necrotic cells or bacterial endotoxin. In addition, our results indicate that apolipoproteins could dramatically abrogate complement fixation on the surface of necrotic cells. These findings suggest that apolipoproteins, besides having known functions in lipid metabolism, also have a role in preventing the initiation of innate immunity, potentially through neutralizing Hyppos from injured cells or exogenous endotoxin.