Anti-endotoxin Role of Lipoproteins

Harris et al (1990) tested the effects of lipoproteins on endotoxin. They found that triglyceriderich VLDL and chylomicrons, as well as cholesterolrich LDL and HDL, and cholesterolfree SOYACAL can protect against endotoxininduced death. These observations suggest a possible role for increased triglyceriderich lipoproteins in the host's defense against endotoxemia and infection.

Low density lipoproteins Inhibit Endotoxin Activation Of Monocytes


Weinstock et al (1992) have studied the relationship of human serum and low density lipoproteins (LDLs) and endotoxin activation of human monocytes. Sera and LDL preparations from four patients with familial hypercholesterolemia were used to demonstrate the inhibition of microbial lipopolysaccharide (LPS) from inducing interleukin1 release. Before LDL removal by immunoapheresis, the patients' sera were able to inactive approximately fivefold more LPS than after LDL removal. The LPSinactivating capacity lost during apheresis could essentially be retrieved in the LDLrich eluate from the immunoadsorption columns. These patients' sera before LDL removal were shown to inactivate amounts of LPS comparable to those inactivated by the sera from three healthy volunteers. LDL prepared by ultracentrifugation showed similar LPS inactivation as LDL prepared by immunoapheresis. It was concluded that the inhibition of LPSinduced monocyte activation by human serum is dependent to a large extent on the LDL fraction. LDLs were demonstrated to inhibit LPS from inducing interleukin1 release by human monocytes.

Low Density Lipoprotein Decreases Endotoxin Toxicity

 High Density Lipoprotein Inhibited LPS Endotoxin Toxicity

Morel et al (1986) noted that bacterial endotoxins (lipopolysaccharides (LPS)) had been reported to be toxic to bovine endothelial cells both in vivo and in vitro. They reported that the presence of plasma low density lipoprotein (LDL) protected bovine endothelial cells from LPSinduced toxicity whereas the presence of LDL actually promoted LPSinduced toxicity to human endothelial cells.

High density lipoprotein also inhibited LPSinduced toxicity to bovine endothelial cells but unlike LDL, did not enhance LPSinduced toxicity to human cells. The toxicity of LPS to human endothelial cells in the presence of LDL required the oxidation of LDL by free radicals produced by the endothelial cells. LDL modified by acetylation enhanced LPSinduced toxicity to human endothelial cells. Polymyxin B, a specific LPS antagonist, inhibited the toxicity of LPS to bovine endothelial cells but not the toxicity of LPS plus LDL to human endothelial cells.

The authors concuded that LDL prevents the toxicity of LPS to bovine endothelial cells by binding the LPS and making it less accessible to the cells. Human endothelial cells are not directly susceptible to LPSinduced toxicity but produce oxygen free radicals in sufficient quantity to oxidize LDL and render the LDLLPS complex recognizable for uptake by a scavenger receptorlike process similar to that for acetylLDL. LPS thus enters the human endothelial cells via this complex and kills the cells. These findings may have important implications for the study of LPSinduced toxicity to endothelial cells in vitro and for understanding the phenomenon in vivo.

High Density Lipoproteins Protect Against Trypanosomes Infection


Rifkin (1991) investigated the role of HDL in protecting against the virulence of the African trypanosomes, protozoa that cause fatal diseases both in humans and livestock. High density lipoproteins from hosts resistant (baboon, human) or susceptible (rabbit, rat) to Trypanosoma brucei infection were isolated and their trypanocidal activity was determined in vitro cell lysis assays. Rabbit and rat HDL were not cytotoxic while baboon and human HDL rapidly lysed trypanosomes within 2 hours at 37 degrees C.

Lipoprotein-Binding Reduces Injurious Effects of Toxic Microbial Metabolites (flucloxacillin, dicloxacillin, ceftriaxone)


Henning et al (1988) found that the unpredictable inactivation of beta-lactam antibiotics (fungal metabolites) (mycotoxins) was due to their being bound to lipoproteins. In vitro inactivation took place within 5 minutes of the addition of the antibiotic to human serum which demonstrates the rapidity and efficiancy of the toxin binding property of lipoproteins.


In Vitro Inactivation of Bacterial Endotoxin by Human Lipoproteins and Apolipoproteins.

Emancipator et al (1992) found that lipoproteins are endotoxin inactivators and this ability of lipoproteins may be modulated by their lipid component (lipidendotoxin interaction) They also noted that apolipoprotein A1 is capable of directly inactivating endotoxin (protein endotoxin interaction).

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