Apolipoproteins modulate the inflammatory response to lipopolysaccharide

Abstract

An increasing body of evidence demonstrates a close interplay between lipoprotein metabolism and sepsis. Sepsis results in an increase of plasma triglycerides within VLDL as a consequence of an enhanced hepatic VLDL production and/or inhibited peripheral and hepatic VLDL clearance. In contrast, sepsis decreases plasma cholesterol within LDL and mainly HDL. The decrease in HDL is accompanied by a loss of mainly apoAI-containing particles, an almost total loss of apoCI, and an increase in apoE-containing HDL, as related to the effect of LPS on a wide range of apolipoproteins, plasma enzymes, lipid transfer factors, and receptors that are involved in HDL metabolism. Reciprocally, all lipoprotein classes have been shown to bind LPS and to attenuate the biological response to LPS in vitro and in rodents. Moreover, triglyceride-rich lipoproteins protect rodents against death from LPS and bacterial sepsis. Accumulating evidence indicates that apolipoproteins such as apoE and apoAI, and not the lipid moieties of the particles, may be responsible for these protective effects of lipoproteins. Therefore, to increase our understanding of the complex interaction between lipoprotein metabolism and sepsis, further studies that address the specific roles of apolipoproteins in sepsis are warranted.

Competition between immune function and lipid transport for the protein apolipophorin III leads to stress-induced immunosuppression in crickets

“…For example, in vertebrates, lipoproteins [e.g. high density lipoprotein (HDL)] are important for both lipid (cholesterol) transport and for sequestering bacterial lipopolysaccharides (LPS) (Berbée et al, 2005;Wendel et al, 2007). During a bacterial challenge, the lipoprotein composition of HDL changes and reverse cholesterol transport declines (Wendel et al, 2007).…”

“…We hypothesize that this transient decline in disease resistance in crickets is caused, at least in part, by physiological interactions between the immune system and lipid transport. These two systems are intertwined in both vertebrates (Berbée et al, 2005;Wendel et al, 2007) and insects (Weers and Ryan, 2006).…”

Mechanisms of Neutrophil Accumulation in the Lungs Against Bacteria

“…Hypercholesterolemia primes PMNs for oxidant and granule protein release (72,73), induces PMN adhesion to and emigration from postcapillary venules (74), and promotes mononuclear cell accumulation in vascular lesions by inducing endothelial chemokines (75,76). The net effect of systemic dyslipidemia on organ-localized inflammation is likely, however, to be complex, as cholesterol loading also impairs leukocyte chemotaxis (77), and lipoproteins, the particles that carry cholesterol in the bloodstream, bind to and neutralize bacterial LPS (78) and inhibit leukocyte signaling responses to multiple TLR ligands (79). Further complicating expectations for the net effect of cholesterol upon inflammation in the lung in particular is the fact that the mechanism of, and requirements for, PMN transmigration from the vascular compartment into the airspace differ substantially from those at work in other organs (3).…”

The apolipoprotein A-I mimetic peptide 4F prevents defects in vascular function in endotoxemic rats

“…These products have been implicated in hemodynamic disturbances in sepsis by reducing peripheral vascular resistance ( 9-14 ). Cardiovascular (CV) failure, characterized by severe hypotension and cardiac dysfunction, is linked to increased mortality in patients with severe sepsis ( 15-17 ).Lipoproteins are thought to play a role in the neutralization/detoxifi cation of endotoxin (18)(19)(20). Low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) bind to LPS and direct it to the liver for metabolism and excretion (18)(19)(20).…”

“…Lipoproteins are thought to play a role in the neutralization/detoxifi cation of endotoxin (18)(19)(20). Low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) bind to LPS and direct it to the liver for metabolism and excretion (18)(19)(20).…”