Public Release: 

Clearing the way for lipopolysaccharide

JCI Journals

The rapid initiation and execution of a host response to pathogens is critical. In the case of Gram-negative bacteria, lipopolysaccharide (LPS), a major constituent of the outer membrane, provokes a potent, generalized inflammatory response in the infected host by virtue of its ability to bind membrane factors present on the surface of macrophages and other cells crucial to host defense. LPS also binds to circulating plasma proteins such as the LPS binding protein (LBP). However, once the response to Gram-negative bacteria is initiated, there is a need to eliminate LPS from the circulation to minimize potential deleterious effects of an unregulated response. The primary means of eliminating LPS is by its incorporation into lipoproteins. Again, LBP plays a role by catalyzing the transfer of LPS from micelles into lipoproteins. In fact, consistent with the role of LBP and lipoproteins in LPS clearance, among the changes seen in the acute phase response are substantial increases in the circulating levels of LBP and serum lipid and lipoproteins. In this issue, Vreugdenhil et al. offer additional insights into LPS clearance, showing that circulating LBP and LPS are predominantly complexed with apoB-associated lipoproteins -- i.e., low-density lipoproteins (LDL) and very low-density lipoproteins (VLDL) -- in normal and septic individuals. While LBP will bind in vitro to apoA-I, a component of HDL, the basis for the preferential in vivo association of LBP with LDL and VLDL appears to result in part from the considerably greater affinity of LBP for apoB than for apoA-I. Furthermore, LBP, when complexed with LDL and VLDL, appears to enhance LPS binding to these lipoproteins. Additional studies of the interactions of LBP and LPS with apoB, apoE, and perhaps other LDL- and VLDL-associated factors should further understanding of specific mechanisms that regulate LPS levels in infection and inflammation.

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