Lipopolysaccharide (LPS)-binding protein mediates LPS detoxification by chylomicrons.
Chylomicrons have been shown to protect against endotoxin-induced lethality. LPS-binding protein (LBP) is involved in the inactivation of bacterial toxin by lipoproteins. The current study examined the interaction among LBP, chylomicrons, and bacterial toxin. LBP was demonstrated to associate with chylomicrons and enhance the amount of LPS binding to chylomicrons in a dose-dependent fashion. In addition, LBP accelerated LPS binding to chylomicrons. This LBP-induced interaction of LPS with chylomicrons prevented endotoxin toxicity, as demonstrated by reduced cytokine secretion by PBMC. When postprandial circulating concentrations of chylomicrons were compared with circulating levels of low density lipoprotein, very low density lipoprotein, and high density lipoprotein, chylomicrons exceeded the other lipoproteins in LPS-inactivating capacity. Furthermore, highly purified lipoteichoic acid, an immunostimulatory component of Gram-positive bacteria, was detoxified by incubation with LBP and chylomicrons. In conclusion, our results indicate that LBP associates with chylomicrons and enables chylomicrons to rapidly bind bacterial toxin, thereby preventing cell activation. Besides a role in the detoxification of bacterial toxin present in the circulation, we believe that LBP-chylomicron complexes may be part of a local defense mechanism of the intestine against translocated bacterial toxin.
Vreugdenhil
Anita C E
AC
Nutrition and Toxicology Research Institute Maastricht, Department of General Surgery, Maastricht University, Maastricht, The Netherlands.
Rousseau
Corine H
CH
Hartung
Thomas
T
Greve
Jan Willem M
JW
van 't Veer
Cornelis
C
Buurman
Wim A
WA
D000209:Acute-Phase Proteins; D001665:Binding Sites; D001692:Biological Transport; D001896:Boron Compounds / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000502:physiology*; D002914:Chylomicrons / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism* / Q000633:toxicity*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008562:Membrane Glycoproteins; D019518:Postprandial Period; D013682:Teichoic Acids / Q000378:metabolism / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D001896:Boron Compounds; D002352:Carrier Proteins; D002914:Chylomicrons; D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D008562:Membrane Glycoproteins; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein; C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; C009900:lipoteichoic acid